Physicochemical and Pharmacokinetic Properties’ Screening of Selected Cardiovascular Agents: an in-silico Approach

Physicochemical and Pharmacokinetic Properties’ Screening of Selected Cardiovascular Agents: an in-silico Approach | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Physicochemical and Pharmacokinetic Properties’ Screening of Selected Cardiovascular Agents: an in-silico Approach Aparna Inamdar, Shweta Pote, Suraj Sawant, Preeti S Salve, Shailendra S. Suryawanshi, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2653667/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cardiovascular (CVS) drugs are medications whose primary effects are experienced by the heart and blood vessels to treat cardiovascular disorders such as coronary artery disease, arrhythmias, high blood-pressure, heart failure and stroke. Evaluation of drug-likeness is a qualitative research approach in drug design that examines the drug-like properties of any chemical compound used as a lead in terms of factors such as oral bioavailability. These ADME parameters can be used widely in drug discovery to optimize the properties needed to convert lead candidates into safe and effective drugs for human use. An approach to estimate the passive gastrointestinal (GI) absorption and blood-brain barrier (BBB) access of drugs is the BOILED-Egg model from Swiss-ADME. In the current study, we virtually screened fifty-five bioactive CVS agents, which twenty-three were newly marketed agents and thirty-two were conventional agents. PubChem database for canonical smile collection, Molsoft server for physicochemical properties and drug-likeness screening, Schrodinger's software for ADME parameters, Microsoft Excel software for Heat-Map analysis, Swiss-ADME database for construction of BOILED-Egg model were utilized. The study results revealed that out of fifty-five screened bioactive drugs, forty-six drugs obeyed Lipinski's rule of five (RO5) and forty-five drugs obeyed Jorgensen's rule of three (RO3), were within recommended ranges of physicochemical and pharmacokinetic properties. Few of the compounds found in the Egg-yolk and Egg-white were predicted to pass the BBB and GI, respectively. It can be concluded that maximum of the screened bioactive drugs are proved to be potent drug candidates with good membrane permeability and oral bioavailability. CVS agents Drug-likeness physicochemical properties pharmacokinetic parameters Lipinski's RO5 Jorgensen’s RO3 BOILED-Egg Figures Figure 1 Figure 2 1. Introduction The advent of medicinal chemistry in 1930’s aided in the development of majority of synthetic drugs. Until 1930, majority of drug research was focused on the study of natural products. There are many diseases that can now be treated with synthetic drugs. As a result, the rapid development of various techniques for the synthesis and purification of a large number of new bioactive compounds is critical (Lima, 2007 ). The drug development process changed dramatically as a result of the development of bio-isosterism in the 1950s and 1980s. Molecular modification was extensively used, beginning with studies of structure-activity relationships (SAR). The biochemical aspect of pathological conditions contributed to the target-based drug design approach in the 1980 (Lima and Barreiro, 2012 ). Pharmaceutical companies developed combinatorial synthesis strategy, which enabled the rapid acquisition of combinatorial libraries, to reduce the amount of time for synthesising and purifying large quantities of new compounds. This also resulted in the development of high-throughput screening (HTS) methods for quickly evaluating compounds (Gershell and Atkins, 2023). Thousands of compounds could be synthesised using combinatorial techniques (Walters et al., 1999 ). Despite extensive efforts to identify the best lead molecule and achieve better results, majority of the compounds were rejected during clinical trials due to pharmacokinetic issues and toxicity (Keller et al., 2006 ). The present study strategy is to identify key points in pharmacokinetic and pharmacodynamic parameters that can be used to establish standards in drug design. With the help of these research techniques, the drug nature and their search become remarkable. This process is also known as drug-likeness or drug-like molecule recognition (Vistoli et al. , 2007). Several rules were proposed to aid in the identification of promising molecules. Lipinski's RO5, developed by Pfizer medicinal chemist Christopher, is the most common and widely used rule. The Lipinski's RO5 is commonly used to screen potentially active compounds from combinatorial libraries that may have good oral absorption and/or permeation (Biswas et al., 2006 ). According to the RO5, poorly absorbed drugs have a pair or several of the following characteristics: More than 500 Dalton molecular weight, partition coefficient (Clog P ) greater than 5 (or Mlog P less than 4.5), more than 5 hydrogen-bond donor groups (HBD) (expressed as the sum of OH and NH groups), and more than 10 hydrogen bond acceptor groups (expressed as the sum of O and N atoms). Since each range in the rule is a multiple of 5, it was given the name Rule of Five (RO5). Biomacromolecules and natural compounds are exempted from this assessment because they do not generally adhere to the Rule of Five (RO5) (Lipinski et al., 2012 ). The Jorgensen Rule of Three is another widely accepted rule for lead like properties of drug and states that the aqueous solubility measured as logS should be greater than − 5.7, the apparent Caco-2 cell permeability should be faster than 22nm/s, and the number of primary metabolites should be less than 7 (Lionta et al., 2014 ). Drug likeness is a qualitative strategy in drug design that looks at the 'drug like' characteristics displayed by a chemical compound selected as a lead in relation to certain elements like bioavailability. Prior to the chemical being manufactured and analysed, it is approximated from the lead's molecular structure. A drug-like molecule has qualities like solubility in both water and fat, as an orally taken medicine needs to pass well beyond the intestinal tract when it is consumed, be carried in aqueous blood, and penetrate the lipid-based bi-layered cell membrane to enter the interior of a cell. Drug candidates should have high biological target potency (high pIC50 values), as this reduces the probability of non-specific, off-target pharmacology at a given concentration. The lipophilic effectiveness of the ligand plays an important role here, as the molecule’s weight directly impacts diffusion, but the smaller the molecular weight, the better its aqueous solubility. Drugs having molecular weights between 200 and 600 Dalton comprise majority of the market (Drug likeness, 2020 ). The science of pharmacokinetic analysis includes absorption, distribution, metabolism, and elimination (ADME) research (ADME, 2020 ). ADME studies examine how a chemical molecule, like a medication substance, is absorbed in the body, distributed to various other organs and tissues and metabolized by individuals. In order to balance the qualities needed to turn lead candidates into medicines that are safe and beneficial for human use, these studies are often used in drug discovery. This particular field of science studies what happens to a drug from the time it is administered until it is eventually eliminated from the body (What is ADME? 2020). The ADME profile is used to determine how a different organ structure impacts the medicine and its functionality when a medicine is administered to the body, how much of it (its bioavailability) actually makes it into the systemic circulation? Absorption, how rapidly is it absorbed? Distribution, which body parts are susceptible to medication distribution? What are the distribution's rate and size? What is the rate at which medicines are converted to metabolites? What is the action's mechanism? Metabolism, what metabolites are generated and are they hazardous or active? Elimination, how quickly and how the substance is eliminated by the excretory system from the body (The role, 2020). A study of the literature revealed that there is a lack of research on virtual screening of cardiovascular medicines till date. Cardiovascular agents are drugs that are generally used to treat the diseases of the heart and blood vessels, including coronary artery disease, arrhythmias, blood clots, high cholesterol, hypertension, hypotension, heart failure, and stroke. Cardiovascular medicines are those that primarily treat cardiovascular disorders or that have their significant effects on the heart or blood vessels. They generally affect the circulatory structural organisations either directly or indirectly through the kidney, autacoids, central nervous system, autonomic nervous system, or hormones that regulate the cardiovascular functions (Cardiovascular agents, 2021). A rapid, convenient, and quickly repeatable approach to estimating the passive gastrointestinal (GI) absorption and blood-brain barrier (BBB) access of drugs and chemical compounds is the BOILED-Egg model from Swiss ADME, which could be useful in the drug-discovery and development processes. This predictive model works by computing the lipophilicity and polarity of small molecules (Daina et al,. 2016) In-silico screening of the physiochemical properties and pharmacokinetic parameters of selected CVS medicines is therefore the focus of the current research endeavour. In the current examination, an attempt has been made to use servers, software, and computational tools to study the drug-like features of cardiovascular medications. 2. Materials And Methods 2.1 Software’s and servers used PubChem database was used for collection of canonical smiles and downloading SDF files (PubChem, 2021), Molsoft software was used for determination of drug likeness (Molsoft, 2021), Swiss ADME database for construction of BOILED-Egg model (Swiss ADME 2023), Schrodinger’s software via Maestro 12.4 interface was used for ADME studies (QikProp, 2021). 2.2 Selected medicinal agents. In the present investigation, we have selected some cardiovascular drugs. The list of medicinal agents selected in study along with their drug class and uses are presented in Table 1 (Tripathi KD, 2018; Recently marketed, 2021). Table 1 List of selected Cardiovascular agents used in the current study Sr. No. Drug name Class Sub-Class Uses 1 Glyceryl trinitrite Anti-anginal agent Vasodilators Angina pectoris. 2 Propranolol Anti-anginal agent Anti-arrhythmic agent Anti-hypertensive agent β- adrenergic blockers Class-II anti-adrenergic agents Angina pectoris, arrhythmia and hypertension. 3 Verapamil Anti-anginal agent Anti-arrhythmic agent Anti-hypertensive agent Calcium channel blockers Angina pectoris, arrhythmia and hypertension. 4 Diltiazem Anti-anginal agent Anti-arrhythmic agent Anti-hypertensive agent Calcium channel blocker Angina pectoris, arrhythmia and hypertension. 5 Nicorandil Anti-anginal agent Potassium channel openers Chest pain caused by angina. 6 Trimetazidine Anti-anginal agent Anti-ischemic(anti-anginal) metabolic agent of the fatty acid oxidation inhibitor Angina (chest pain). 7 Quinidine Anti-arrhythmic agent Class-I agents membrane stabilizing agent Arrhythmia. 8 Disopyramide Anti-arrhythmic agent Class-I membrane stabilizing agent Arrhythmia. 9 Amiodarone Anti-arrhythmic agent Class III agents widening action potential Ventricular arrhythmias and atrial fibrillation. 10 Dofetilide Anti-arrhythmic agent Class III agents widening action potential Irregular heartbeat (including atrial fibrillation or atrial flutter). 11 Chlorthalidone Anti-hypertensive agent Thiazide diuretics High blood pressure and fluid retention caused by various conditions. 12 Furosemide Anti-hypertensive agent High ceiling diuretics High blood pressure, heart failure and oedema. 13 Spironolactone Anti-hypertensive agent Aldosterone antagonist Hyperaldosteronism caused by various conditions, including liver, heart or kidney disease. 14 Indapamide Anti-hypertensive agent Thiazide diuretics Hypertension. 15 Captopril Anti-hypertensive agent ACE inhibitors Used alone or in combination with other medications to treat high blood pressure and heart failure. 16 Losartan Anti-hypertensive agent Angiotensin (AT 1 ) receptor blockers High blood pressure and heart failure. 17 Aliskiren Anti-hypertensive agent Direct renin inhibitors Used alone or in combination with some medications to treat high blood pressure 18 Prazosin Anti-hypertensive agent α- adrenergic blockers Used alone or in combination with other medications to treat high blood pressure 19 Clonidine Anti-hypertensive agent Central sympatholytic Hypertension. 20 Hydralazine Anti-hypertensive agent Arteriolar Dilator Hypertension. 21 Lovastatin Anti-hyperlipidemic agent 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) Used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke 22 Pravastatin Anti-hyperlipidemic agent 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) Used to lower cholesterol levels. 23 Bezfibrate Anti-hyperlipidemic agent Lipoprotein lipase activators peroxisome proliferator-activated receptors alpha (PPARα agonists: Fibrates) Hyperlipidemia. 24 Nicotinic acid Anti-hyperlipidemic agent Lipolysis and triglyceride synthesis inhibitors Niacin deficiency (pellagra). 25 Ezetimibe Anti-hyperlipidemic agent Sterol absorption inhibitor Used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of cholesterol 26 Pentoxifylline Hemorrheologic agents Rheological agents Reduces leg pain caused by poor blood circulation. 27 Cyclandelate Vasodilators Vasodilators Various blood vessel diseases, arteriosclerosis. 28 Cilostazol Platelet-aggregation inhibitors. Phosphodisterase-3 inhibitors Reduces the symptoms of intermittent claudication. 29 Clopidogrel Platelet-aggregation inhibitors. Antiplatelet drugs Prevents platelets from sticking together and forming blood clot. 30 Digoxin Digitalis glycosides. Cardiac glycosides Arrhythmia and atrial fibrillation. 31 Digitoxin Cardiac glycosides. Cardiac glycosides Heart failure 32 Dopamine Inotropic agents. Sympatho-mimetics Symptoms of low blood pressure, low cardiac output and improves blood flow to the kidneys. 33 Verquvo Drugs for chronic heart failure Soluble guanylate cyclase activator Chronic heart failure 34 Orladeyo Anti-anginal agent Plasma kallikrein inhibitor Hereditary angioedema. 35 Vyndaquel TTR stabilizing agent protein transthyretin receptor (TTR) stabilizer Cardiomyopathy caused by transthyretin mediated amyloidosis (ATTR-CM) in adults. 36 Yupelri Anti-cholinergic agent Anti-cholinergics Chronic obstructive pulmonary disease (COPD). 37 Giapreza Vasoconstrictor Synthetic vasoconstrictor peptide Increases blood pressure in adults with septic or other distributive shock. 38 Rhopressa Ocular anti-hypertensive agent RHO kinase enzyme inhibitor Glaucoma (ocular hypertension) 39 Vyzulta Ocular anti-hypertensive agent Prostaglandin F-receptor agonist Open-angle glaucoma (ocular hypertension). 40 Uptravi Anti-thrombic agents Selective non-proteinoid IP prostacyclin receptor agonists. Pulmonary arterial hypertension. 41 Kengreal Anti-thrombic agents P 2 Y 12 purinoreceptor antagonist Prevents the formation of harmful blood clots in the coronary arteries for adult patients undergoing percutaneous coronary intervention 42 Corlanor Inhibiting cardiac pacemaker current (I f ) inhibitors Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers Reduces hospitalization from worsening heart failure. 43 Savaysa Direct factor Xa inhibiting agent Selective inhibitor of factor Xa Reduces the risk of stroke due to systemic embolism in patients with atrial fibrillation. 44 Lumason Image enhancing agent Inert image enhancing agent and has no pharmacologic effect. For patients whose ultrasound image of the heart (echocardiograms) is hard to detect with ultrasound waves. 45 Zontivity (PAR-1) antagonist. Protease-activated receptor-1 (PAR-1) antagonists. Reduces the risk of heart attacks and stroke in high-risk patients. 46 Opsumit Endothelin receptor antagonists Endothelin receptor antagonists. Pulmonary arterial hypertension (PAH) in adults. 47 Adempas Soluble guanylate cyclase (sGC) stimulators Soluble guanylate cyclase (sGC) stimulators Pulmonary hypertension. 48 Eliquis Factor Xa inhibiting agent Indirect inhibitor of platelet aggregation induced by thrombin Reduces the risk of stroke and systemic embolism in patients with atrial fibrillation. 49 Juxtapid Microsomal triglyceride transfer protein (MTP) inhibitor Cholesterol-lowering medications Reduces low-density lipoprotein (LDL) cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). 50 Belviq CNS stimulants Anorexiants 5-HT 2 C receptor agonists 5-HT 2 C receptor activator Chronic weight management. 51 Zioptan Anti-glucomic agent Prostaglandin agonists Selective agonist prostaglandin F-receptor Reduces elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension 52 Firazyr Bradykinin B2 receptor antagonists Bradykinin B2 receptor antagonist Hereditary angioedema (HAE) acute attacks in people aged 18 years and older. 53 Brilinta Oral anti-platelet agents Direct-acting P2Y12-receptor antagonist Reduces cardiovascular death and heart attack in patients with acute coronary syndromes (ACS). 54 Xarelto Factor Xa inhibitor Factor Xa inhibitor Reduces the risk of blood clots, deep vein thrombosis (DVT), and pulmonary embolism (PE) following knee or hip replacement surgery. 55 Edarbi Angiotensin II blocker Selective AT 1 subtype angiotensin II receptor antagonist. Hypertension in adults. From the therapeutic substances belonging to the class of CVS, we have identified a number of pharmaceuticals for the current research project. The reference books and research articles provide us the in-depth information regarding cardiovascular agents that is presented below. 3. Methodology 3.1 Evaluation of the drug-likeness of selected phytoconstituents Drug likeness studies were conducted by utilizing Molsoft server by Navigating to https://molsoft.com/mprop/ in Google or Chrome. It will redirect you to Molsoft. Which will give the drug likeness profile of drug molecules with the following information. Molecular Formula of the compound, Weight of Molecule, Number of hydrogen bond acceptors, Number of hydrogen bond donors, Log P, Polar surface area of a molecule (PSA), Drug Likeness Score. 3.2 Determination of pharmacokinetics of selected phytoconstituents ADME studies are carried out using Schrodinger’s software vi a Maestro 12.4 interface. Various parameters were determined with the help of Schrodinger’s software (QikProp, 2021). 3.3 Determination of BBB and GI permeability of selected medicinal agents via BOILED-Egg model For the prediction of the permeability of the selected CVS agents through the BBB and passive absorption of the drugs via GI tract the BOILED-Egg model from Swiss ADME database was utilized. 4. Results And Discussion 4.1 Determination of physiochemical properties and drug likeness of selected medicinal agents A qualitative concept of drug likeness is used in drug design to assess what a "druglike" compound is in terms of factors such as bioavailability. In this study, various drug likeness parameters of the conventional and recently marketed bioactive drugs were calculated in order to understand the effect of physicochemical properties on bioavailability patterns in human body. The permissible ranges of physicochemical parameters for good oral bioavailability of drugs are 4.1.1 MW : Molecular weight of the drug should be lesser than (< 500 Daltons). 4.1.2 HBA : Hydrogen Bond acceptors should be within ten (≤ 10). 4.1.3 HBD : Hydrogen Bond donors should be within five (≤ 5). 4.1.4 Log P : Partition coefficient of the drug (≤ 5). 4.1.5 PSA : Polar surface area of the drug (90–140Å). 4.1.6 RO5 : Rule of five violations (≤ 1). Molsoft online server was used to screen the selected drugs’ druggable characteristics. The results are displayed in Table 2 . Table 2 The physicochemical properties and drug likeness data of selected CVS drugs Sr. No Drug Name MW ( 0) 1 Glyceryl trinitrite 179.02 9 0 -1.47 114.46 0 0.19 2 propranolol 259.16 3 2 3.42 34.97 0 0.93 3 Verapamil 454.28 6 0 3.87 51.62 0 0.92 4 Diltiazem 414.16 6 0 2.66 47.18 0 1.19 5 Nicorandil 211.06 5 1 -0.77 81.56 0 1.07 6 Trimetazidine 266.16 5 1 1.40 39.00 0 0.57 7 Quinidine 324.18 4 1 3.21 35.65 0 0.82 8 Disopyramide 339.23 3 2 2.64 46.41 0 1.15 9 Amiodarone 645.02 4 0 7.82 32.40 2 1.16 10 Dofetilide 441.14 6 2 1.04 95.19 0 O.79 11 Chlorthalidone 257.11 3 1 2.68 43.86 0 0.29 12 Furosemide 330.01 6 4 2.10 96.54 0 0.72 13 Spironolactone 416.20 5 0 2.40 47.39 0 1.35 14 Indapamide 365.06 4 3 2.19 79.28 0 0.73 15 Captopril 217.08 4 2 0.41 45.63 0 -0.20 16 Losartan 422.16 5 2 4.54 78.76 0 0.14 17 Aliskiren 551.39 7 6 2.70 119.40 2 0.84 18 Prazosin 383.16 6 2 1.75 81.90 0 0.97 19 Clonidine 229.02 1 2 3.36 30.62 0 1.46 20 Hydralazine 160.07 3 3 0.85 58.01 0 0.53 21 Lovastatin 404.26 5 1 4.20 56.73 0 0.98 22 Pravastatin 424.25 7 4 2.22 97.80 0 0.93 23 Bezfibrate 361.11 4 2 2.96 59.12 0 1.07 24 Nicotinic acid 123.03 3 1 0.51 38.16 0 0.30 25 Ezetimibe 409.15 3 2 3.98 49.14 0 0.77 26 Pentoxifylline 278.14 4 0 -0.23 57.34 0 0.92 27 Cyclandelate 276.17 3 1 3.38 36.01 0 0.48 28 Cilostazol 369.22 5 1 2.99 72.35 0 0.85 29 Clopidogrel 321.06 4 0 3.78 25.12 0 1.05 30 Digoxin 780.43 14 6 1.09 160.20 3 0.89 31 Digitoxin 764.43 13 5 2.37 144.58 2 1.05 32 Dopamine 153.08 3 4 -0.25 54.49 0 0.09 33 verquvo 426.14 6 5 1.60 114.37 0 0.77 34 Orladeyo 562.21 5 4 4.88 85.60 1 1.38 35 Vyndaquel 502.09 10 7 1.55 138.22 2 -0.17 36 Yupelri 597.33 6 3 3.21 87.75 1 2.09 37 Giapreza 1045.53 15 16 -4.34 328.16 3 -0.21 38 Rhopressa 453.21 5 3 3.70 75.09 0 0.70 39 Vyzulta 507.28 8 3 3.15 116.10 1 0.48 40 Uptravi 496.21 6 1 3.10 85.65 0 0.95 41 Kengreal 774.95 17 7 -0.90 198.56 3 0.32 42 Corlanor 468.26 6 0 2.91 52.04 0 1.57 43 Savaysa 541.18 8 3 1.69 113.01 1 1.82 44 Lumason 140.36 0 0 1.84 0.00 0 -1.48 45 Zontivity 492.24 5 1 5.85 63.59 1 0.65 46 Opsumit 585.96 9 2 4.39 107.71 1 1.04 47 Adempas 422.16 6 4 1.55 105.33 0 0.27 48 Eliquis 459.19 5 2 2.25 88.45 0 0.44 49 Juxtapid 693.28 3 2 8.24 52.32 2 1.04 50 Belviq 231.06 1 2 2.63 12.38 0 -0.02 51 Zioptan 452.24 5 2 5.42 59.09 1 0.81 52 Firazyr 1303.66 18 22 -7.76 418.24 3 0.14 53 Brilinta 522.19 9 4 2.36 109.99 1 1.30 54 Xarelto 435.07 6 1 1.63 75.50 0 0.80 55 Edarbi 568.16 10 1 4.28 117.16 1 0.76 The results displayed in Table 2 exhibit that maximum of the selected cardiovascular drugs possessed acceptable number of acceptors of hydrogen bonds (≤ 10), hydrogen bond donors (≤ 5), partition coefficients within recommended ranges (≤ 5), and polar surface areas (90–140Å) within permissible ranges. Few drugs do not comply with the given standard values for molecular weight of the drug (< 500 Daltons). Thus, the selected CVS drugs show good oral bioavailability as most of the drugs obeyed Lipinski’s rule of 5 (≤ 1) and displayed drug likeness score above 0. 4.2 Determination of pharmacokinetic properties of selected medicinal agents The purpose of ADME studies is to learn how well a substance (a drug compound) is processed by a human cell. In this study, numerous ADME parameters of the screened substances were determined in order to comprehend the impact of physicochemical and pharmacokinetic properties on bioavailability patterns in the human body, further all parameters of each of the selected CVS agents were subjected for the Heat-Map analysis and its represented in the Table 3 . The following parameters are included in this study: 4.2.1 CNS ( 500 great) Predicted central nervous system activity on a -2 (inactive) to + 2 (active) scale. This parameter indicates the lipophilicity of the drugs, as non-lipophilic compounds do not normally traverse the cell wall membrane passively, whereas highly lipophilic molecules risk becoming stuck within the membranes. 4.2.2 Mol_MW (130.0 to 725.0 dalton) This parameter provides molecular weight of the molecule as lower MW 500D compound shows higher lipophilicity and high membrane permeability. 4.2.3 Dipole (1.0 to 12.5) This parameter provides the molecule's calculated dipole moment, which is useful for determining the polarity of the chemical bond. 4.2.4 Volume (500.0 to 2000.0) This parameter serves details about the total accessible solvent volume in terms of cubic angstrom by utilizing a probe with a radius of 1.4 Å. 4.2.5 QplogPC16 (4.0 to 18.0) This parameter helps in predicting the distribution of drug in two immiscible phases i.e partition coefficient of hexadecane/gas. 4.2.6 QplogPoct (8.0 to 35.0) The parameter QplogPoct aids to predict the distribution of drug in two immiscible phases i.e; octanol/gas partition coefficient. 4.2.7 QplogPw (4.0 to 45.0) This parameter assists in predicting the distribution of drug in two immiscible phases i.e; water/gas partition coefficient. 4.2.8 QplogPo/w (-2.0 to 6.5) This parameter indicates the distribution of drug in two immiscible phases i.e; partition coefficient of octanol/water. 4.2.9 QplogS (-6.5 to 0.5) It demonstrates the expected water solubility, where, S is the concentration of the solute which is in equilibrium with the crystalline solid’s saturated solution. 4.2.10 CIQPlogS (-6.5 to 0.5) It indicates the conformation-independent log S, wherein S in terms of mol dm -3 is the concentration of the solute present in the saturated solution that is in equilibrium with the crystalline solid. 4.2.11 QPlogHERG (Concentration below − 5) This parameter predicts the IC 50 value for blocking the human ether-a-go-go related genes (HERG) K + channels. 4.2.12 QPPCaco ( 500 great) It’s the expected apparent Caco-2 cell permittivity in nanometer range per second. Caco-2 cells are a model for the gut-blood barrier and are an immortalised cell line of human colorectal adenocarcinoma cells. QikProp predictions are for passive transportation. 4.2.13 QplogBB (Brain/blood partition coefficient predicted; -3.0 to 1.2) Since most of the drugs are taken orally, these values are CNS negative. For example, both serotonin and dopamine are CNS negative as they are too hydrophilic to pass the blood-brain barrier. 4.2.14 QplogKp (-8.0 to 1.0) This parameter aids in estimating skin penetration (logKp) for transportation of the compound through mammalian epidermis. 4.2.15 QPPMDCK (Predicted apparent Madin-Darby canine kidney; 500 great) MDCK cell permeability is depicted in terms of nm/sec. MDCK cells are considered to be a good mimic for the BBB. QikProp predictions are for non-active transport. 4.2.16 QplogKhsa (-1.5 to 1.5) Because of the availability of more binding sites on HSA, this parameter aids in drug prediction. HSA is a bioavailable, agglomerated, and un-glycosylated monomeric protein that performs primarily as a transport protein for steroids, essential fats, and thyroid stimulating hormone, and plays an important role in extracellular fluid volume stabilization. 4.2.17 %HOA (> 80% high, < 25% poor) On a scale of 0 to 100%, human oral absorption was predicted. A quantifiable model of multiple linear regression is employed to make the prediction. Because they both measure the same property, this property usually correlates well with Human Oral Absorption. 4.2.18 PSA (7.0-200.0 A 2 ) The surface sum of all polar atoms and molecules, predominantly oxygen and nitrogen, including their connected hydrogen atoms, is defined as the polar surface area. As a result, this parameter provides information about the Van-Der Waals total surface area of polar both nitrogen and oxygen atoms. 4.2.19 RO5 (Maximum is 4 violations) Lipinski’s rule of five RO5 has been separated into five parts. Those are: mol_MW < 500, PSA 07-200 A 2 , donorHB ≤ 5. accptHB ≤ 10. Compounds that satisfy these rules are considered drug-like molecule. (The “five” refers to the limits, which are multiples of five.) 4.2.20 RO3 (Maximum number allowed is 3 violations) Jorgensen’s rule of three RO3. The three rules are: QplogS should be >-5.7, QPPCaco should be > 22 nm/s, #Primary Metabolites should be < 7. Compounds that violate fewer rules (preferably no) of these regulations are much more probable to be orally convenient. The colors blue, yellow, green, and red in Table 3 of the heat-map analysis of the pharmacokinetic properties of selected CVS agents represent the lowest, moderate, highest, and extremely high values (corresponding to drugs that violated the particular rule), respectively. The results depicts that most of the selected CVS agents had good oral absorptivity as very few of the drugs violated Lipinski’s RO5 and Jorgensen’s RO3 and nearly all of the compounds showed 100% of human oral absorption. All the selected CVS drugs have displayed molecular weights, dipole moments, presumed partition coefficient of water/gas, lying between recommended ranges. It was found out that majority of the drugs displayed permissible values for certain parameters such as total solvent-accessible volume, predicted partition coefficient of hexadecane/gas, predicted partition coefficient of octanol/gas, predicted water solubility, aqueous solubility that is not dependent on conformation, predicted MDCK cells penetrability, predicted skin penetrability, the Vander Waal’s total surface area of polar atoms or molecules such as nitrogen and oxygen atoms and prediction of drug’s ability to bind to human serum albumin proteins. It was seen that only few drugs comply with the IC 50 values required for blocking of HERG K + channels and few drugs showed results lying between the recommended ranges for CNS activity. Thus, the results demonstrated that most of the selected CVS drugs had accountable values for all parameters of pharmacokinetic studies and are therefore regarded powerful drug candidates with great vascular permeability and bioavailability. 4.3 Determination of BBB and GI permeability of Selected medicinal agents via BOILED-Egg model According to the results displayed in the Table 4 , few of the compounds that were found in the Egg-yolk were predicted to pass through the blood-brain barrier (BBB), and those drugs that were found in the Egg-white were predicted to be passively absorbed through the gastro-intestinal (GI) tract, whereas the drugs that are observed as a blue dot are predicted to be effluated from the central nervous system by p-glycoprotein, and drugs that are observed as a red dot were predicted to be not-effluated from central nervous system by p-glycoprotein. 5. Conclusion The physicochemical and pharmacokinetic properties of a number of chosen CVS agents were virtually assessed. A total of fifty-five bioactive components underwent screening for drug likeness, physiochemical properties and ADME parameters. There were twenty-three recently marketed medications and thirty-two conventional drugs in all. Based on the results, forty-six drugs obeyed Lipinski's RO5 and forty-five drugs obeyed Jorgensen’s RO3 wherein the physicochemical and pharmacokinetic parameters were within the recommended ranges. Around thirteen drugs were found in the Egg-yolk that were predicted to pass the BBB and twenty-five drugs found in the egg-white that were predicted to be passively absorbed through the GI tract. Therefore, the evaluated medicines reveal to be powerful drug candidates with strong membrane permeability and bioavailability. This study can be used for optimizing the marketed formulations and repurposing of the drugs. Declarations Acknowledgements We would like to thank Principal and Vice Principal, KLE College of Pharmacy, Belagavi for providing us the research facilities and support for our research work. Conflict of Interest “The authors declare no conflict of interest.” “This article contains Supplementary Material” References Lima LM (2007) Modern medicinal chemistry. Challenges and Brazilian contribution. Quim Nova 30:1456–1468 Lima L, Barreiro E (2012) Bioisosterism. A useful strategy for molecular modification and drug design. Curr Med Chem 12:23–49 Gershell LJ, Atkins JH (2003) A brief history of novel drug discovery technologies. Nat Rev Drug Discov 2:321–327 Walters WP, Murcko A, Murcko MA (1999) Recognizing molecules with drug-like properties. Curr Opin Chem Biol 3:384–387 Keller TH, Pichota A, Yin Z (2006) A practical view of “druggability. Curr Opin Chem Biol 10:357–361 Vistoli G, Pedretti A, Testa B (2008) Assessing drug-likeness - what are we missing? Drug Discov Today 13:285–294 Biswas D, Roy S, Sen S (2006) A simple approach for indexing the oral druglikeness of a compound: Discriminating druglike compounds from nondruglike ones. J Chem Inf Model 46:1394–1401 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 64:4–17 Lionta E, Spyrou G, Vassilatis D, Cournia Z (2014) Structure-Based Virtual Screening for Drug Discovery: principles, applications and Recent Advances. Curr Top Med Chem 14:123–138 Drug likeness (2020) Available via https://en.wikipedia.org/wiki/Druglikeness , accessed10June2021. ADME (2020) Available via https://en.wikipedia.org/wiki/ADME , accessed12June2021. Gleichmann N What is ADME? 2020. Technology networks drug discovery. Available via https://www.technologynetworks.com/drug-discovery/articles/what-is-adme-336683 , accessed15June2021. The role of ADME and Toxicology studies in drug discovery & development (2020) Available via https://www.thermofisher.com/blog/connectedlab/the-role-of-adme-toxicology-studies-in-drug-discovery-development/ , accessed18June2021. Daina A, Zoete V.: A boiled-egg to predict gastrointestinal absorption and brain penetration of small molecules. Chem Med Chem. 11(11), 1117-21 (6 Jun 2016). Cardiovascular agents (2020) Available via https://www.drugs.com/drug-class/cardiovascular-agents.html , accessed21may2021. PubChem Database. Available via http://pubchem.ncbi.nlm.nih.gov/ , accessed21May2021. Molsoft Server. Available via https://www.molsoft.com/ , accessed25may2021. Swiss ADME, Database http://www.swissadme.ch/index.php# , aaccessed30Oct2021. Tripathi KD Cardiovascular drugs. Essentials of medical pharmacology, 8th ed. New Delhi, India: Jaypee brothers’ medical publishers. P.257 – 80; 521–604; 659 – 94 (June 2018) Recently marketed cardiovascular agents. Available via http://wayback.archiveit.org/7993/20170111002417/http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/default.htm , accessed03 June 2021 QikProp Descriptors and Properties (2012) Update 2. Available via http://gohom.win/ManualHom/Schrodinger/Schrodinger_2012_docs/general/qikprop_props.pdf , accessed08 July 2021 Tables Tables 3-4 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table3.docx Table4.docx Supplementryfile1.docx Supplementryfile2.csv Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2653667","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":180736204,"identity":"61ad797e-8ec4-45a6-a12b-ec64666fa289","order_by":0,"name":"Aparna Inamdar","email":"","orcid":"","institution":"KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Aparna","middleName":"","lastName":"Inamdar","suffix":""},{"id":180736206,"identity":"a6e1b2c2-765d-4c74-b3c7-d6774856bd74","order_by":1,"name":"Shweta Pote","email":"","orcid":"","institution":"KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shweta","middleName":"","lastName":"Pote","suffix":""},{"id":180736208,"identity":"bda1cc3e-4c13-4d96-8142-16e06b12870a","order_by":2,"name":"Suraj Sawant","email":"","orcid":"","institution":"KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Suraj","middleName":"","lastName":"Sawant","suffix":""},{"id":180736209,"identity":"5dc7225a-d03e-4a68-9a3d-b87b226b2f87","order_by":3,"name":"Preeti S Salve","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABCElEQVRIie3Qv0rEMBzA8ZRAugRde4j4Cr+j0FLOP69yoZBux8ktFaR0ylR0vcfII0QCN1W69rYronNd1EHU3E2HkHJuDvkOIYR8+IUg5HL92wChI4S8rpzv9tvwsFDmGjG3xiUcTNCOkNFBJD7RD0/9vDgjQbq6WcL5LPYfnyXKJ6y0kOSOp6BAj0XA+VoCXyRVFrWozqwEahoFCpQnaB2tN6CZVJy0ntAD5Pj9Q0FxJWjzdr2BbyabF0O+hggl5scwE35FPAmKyXY7pbSTpCJhUINOhS/C0RLSBbRmynSVhTYSU9z1+WdxcY9x91rllzNozJT+dnJqfdjvg+ne+ificrlcrr1+ACTxXohAR+5xAAAAAElFTkSuQmCC","orcid":"","institution":"KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Preeti","middleName":"S","lastName":"Salve","suffix":""},{"id":180736210,"identity":"b2ed3d7d-5264-4658-ab73-396e0fc0c700","order_by":4,"name":"Shailendra S. Suryawanshi","email":"","orcid":"","institution":"KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shailendra","middleName":"S.","lastName":"Suryawanshi","suffix":""},{"id":180736211,"identity":"9e417391-5db0-4008-b8e3-a24c1fa42707","order_by":5,"name":"Mahesh Palled","email":"","orcid":"","institution":"KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mahesh","middleName":"","lastName":"Palled","suffix":""}],"badges":[],"createdAt":"2023-03-04 04:29:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2653667/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2653667/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":34042145,"identity":"79f556c9-7176-4d9e-8212-374b3bd9b4ee","added_by":"auto","created_at":"2023-03-10 00:05:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":77522,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLipinski’s RO5\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMW: Molecular weight, Log P; partition coefficient/lipophilicity, HBA and HBD; hydrogen bond acceptors and donor\u003c/em\u003e\u003c/p\u003e","description":"","filename":"F1.png","url":"https://assets-eu.researchsquare.com/files/rs-2653667/v1/16dfd9f079f2192ebd9ed974.png"},{"id":34041222,"identity":"8a67a8c5-1cc3-4f22-bc64-2f7998e50454","added_by":"auto","created_at":"2023-03-09 23:57:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":46008,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBOILED-Egg representation of all CVS agents\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDots situated in BOILED-Egg's yolk are those drugs that are predicted to passively permeate through the blood-brain barrier (BBB); dots situated in the BOILED-Egg's white are those drugs that are predicted to be passively absorbed by the gastrointestinal tract (GIT); blue dots represents those drugs that are predicted to be effluated from the central nervous system (CNS) by the P-glycoprotein; red dots represents those drugs that are predicted not to be effluated from the central nervous system by the P-glycoprotein.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"F2.png","url":"https://assets-eu.researchsquare.com/files/rs-2653667/v1/17ebc5fc774db441d665f863.png"},{"id":44957843,"identity":"201658ee-0d6c-4aad-aaae-0d637ff594fe","added_by":"auto","created_at":"2023-10-20 02:37:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":792484,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2653667/v1/ea4e11e8-f0ca-4137-8a57-e29a664018fb.pdf"},{"id":34041226,"identity":"68c4ccae-a443-4742-8ac6-b0a3b2dd2aca","added_by":"auto","created_at":"2023-03-09 23:57:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":67432,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-2653667/v1/21c2338376809e7a7f359d27.docx"},{"id":34041227,"identity":"3c42049c-8812-4d87-ac6b-18fcec5667a1","added_by":"auto","created_at":"2023-03-09 23:57:44","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":470695,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-2653667/v1/ad77c34e0a35edbeebd344a5.docx"},{"id":34042146,"identity":"b252c5f8-3ce1-402b-b81c-3744a2920519","added_by":"auto","created_at":"2023-03-10 00:05:44","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":49657,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementryfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-2653667/v1/426a27dc5190b353f3333f11.docx"},{"id":34041224,"identity":"f650ce97-2f36-444d-a8a6-ee3eab19e93a","added_by":"auto","created_at":"2023-03-09 23:57:44","extension":"csv","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":18846,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementryfile2.csv","url":"https://assets-eu.researchsquare.com/files/rs-2653667/v1/7bd96ccba132e7e223f74ca4.csv"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePhysicochemical and Pharmacokinetic Properties’ Screening of Selected Cardiovascular Agents: an in-silico Approach\u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe advent of medicinal chemistry in 1930\u0026rsquo;s aided in the development of majority of synthetic drugs. Until 1930, majority of drug research was focused on the study of natural products. There are many diseases that can now be treated with synthetic drugs. As a result, the rapid development of various techniques for the synthesis and purification of a large number of new bioactive compounds is critical (Lima, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). The drug development process changed dramatically as a result of the development of bio-isosterism in the 1950s and 1980s. Molecular modification was extensively used, beginning with studies of structure-activity relationships (SAR). The biochemical aspect of pathological conditions contributed to the target-based drug design approach in the 1980 (Lima and Barreiro, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePharmaceutical companies developed combinatorial synthesis strategy, which enabled the rapid acquisition of combinatorial libraries, to reduce the amount of time for synthesising and purifying large quantities of new compounds. This also resulted in the development of high-throughput screening (HTS) methods for quickly evaluating compounds (Gershell and Atkins, 2023). Thousands of compounds could be synthesised using combinatorial techniques (Walters et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e). Despite extensive efforts to identify the best lead molecule and achieve better results, majority of the compounds were rejected during clinical trials due to pharmacokinetic issues and toxicity (Keller et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2006\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe present study strategy is to identify key points in pharmacokinetic and pharmacodynamic parameters that can be used to establish standards in drug design. With the help of these research techniques, the drug nature and their search become remarkable. This process is also known as drug-likeness or drug-like molecule recognition (Vistoli \u003cem\u003eet al.\u003c/em\u003e, 2007). Several rules were proposed to aid in the identification of promising molecules. Lipinski's RO5, developed by Pfizer medicinal chemist Christopher, is the most common and widely used rule. The Lipinski's RO5 is commonly used to screen potentially active compounds from combinatorial libraries that may have good oral absorption and/or permeation (Biswas et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). According to the RO5, poorly absorbed drugs have a pair or several of the following characteristics: More than 500 Dalton molecular weight, partition coefficient (Clog\u003cem\u003eP\u003c/em\u003e) greater than 5 (or Mlog\u003cem\u003eP\u003c/em\u003e less than 4.5), more than 5 hydrogen-bond donor groups (HBD) (expressed as the sum of OH and NH groups), and more than 10 hydrogen bond acceptor groups (expressed as the sum of O and N atoms). Since each range in the rule is a multiple of 5, it was given the name Rule of Five (RO5). Biomacromolecules and natural compounds are exempted from this assessment because they do not generally adhere to the Rule of Five (RO5) (Lipinski et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2012\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe Jorgensen Rule of Three is another widely accepted rule for lead like properties of drug and states that the aqueous solubility measured as logS should be greater than \u0026minus;\u0026thinsp;5.7, the apparent Caco-2 cell permeability should be faster than 22nm/s, and the number of primary metabolites should be less than 7 (Lionta et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDrug likeness is a qualitative strategy in drug design that looks at the 'drug like' characteristics displayed by a chemical compound selected as a lead in relation to certain elements like bioavailability. Prior to the chemical being manufactured and analysed, it is approximated from the lead's molecular structure. A drug-like molecule has qualities like solubility in both water and fat, as an orally taken medicine needs to pass well beyond the intestinal tract when it is consumed, be carried in aqueous blood, and penetrate the lipid-based bi-layered cell membrane to enter the interior of a cell.\u003c/p\u003e \u003cp\u003eDrug candidates should have high biological target potency (high pIC50 values), as this reduces the probability of non-specific, off-target pharmacology at a given concentration. The lipophilic effectiveness of the ligand plays an important role here, as the molecule\u0026rsquo;s weight directly impacts diffusion, but the smaller the molecular weight, the better its aqueous solubility. Drugs having molecular weights between 200 and 600 Dalton comprise majority of the market (Drug likeness, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe science of pharmacokinetic analysis includes absorption, distribution, metabolism, and elimination (ADME) research (ADME, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). ADME studies examine how a chemical molecule, like a medication substance, is absorbed in the body, distributed to various other organs and tissues and metabolized by individuals. In order to balance the qualities needed to turn lead candidates into medicines that are safe and beneficial for human use, these studies are often used in drug discovery. This particular field of science studies what happens to a drug from the time it is administered until it is eventually eliminated from the body (What is ADME? 2020).\u003c/p\u003e \u003cp\u003eThe ADME profile is used to determine how a different organ structure impacts the medicine and its functionality when a medicine is administered to the body, how much of it (its bioavailability) actually makes it into the systemic circulation? Absorption, how rapidly is it absorbed? Distribution, which body parts are susceptible to medication distribution? What are the distribution's rate and size? What is the rate at which medicines are converted to metabolites? What is the action's mechanism? Metabolism, what metabolites are generated and are they hazardous or active? Elimination, how quickly and how the substance is eliminated by the excretory system from the body (The role, 2020).\u003c/p\u003e \u003cp\u003eA study of the literature revealed that there is a lack of research on virtual screening of cardiovascular medicines till date. Cardiovascular agents are drugs that are generally used to treat the diseases of the heart and blood vessels, including coronary artery disease, arrhythmias, blood clots, high cholesterol, hypertension, hypotension, heart failure, and stroke. Cardiovascular medicines are those that primarily treat cardiovascular disorders or that have their significant effects on the heart or blood vessels. They generally affect the circulatory structural organisations either directly or indirectly through the kidney, autacoids, central nervous system, autonomic nervous system, or hormones that regulate the cardiovascular functions (Cardiovascular agents, 2021).\u003c/p\u003e \u003cp\u003eA rapid, convenient, and quickly repeatable approach to estimating the passive gastrointestinal (GI) absorption and blood-brain barrier (BBB) access of drugs and chemical compounds is the BOILED-Egg model from Swiss ADME, which could be useful in the drug-discovery and development processes. This predictive model works by computing the lipophilicity and polarity of small molecules (Daina \u003cem\u003eet al,.\u003c/em\u003e 2016)\u003c/p\u003e \u003cp\u003e \u003cem\u003eIn-silico\u003c/em\u003e screening of the physiochemical properties and pharmacokinetic parameters of selected CVS medicines is therefore the focus of the current research endeavour. In the current examination, an attempt has been made to use servers, software, and computational tools to study the drug-like features of cardiovascular medications.\u003c/p\u003e"},{"header":"2. Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Software\u0026rsquo;s and servers used\u003c/h2\u003e \u003cp\u003ePubChem database was used for collection of canonical smiles and downloading SDF files (PubChem, 2021), Molsoft software was used for determination of drug likeness (Molsoft, 2021), Swiss ADME database for construction of BOILED-Egg model (Swiss ADME 2023), Schrodinger\u0026rsquo;s software via Maestro 12.4 interface was used for ADME studies (QikProp, 2021).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Selected medicinal agents.\u003c/h2\u003e \u003cp\u003eIn the present investigation, we have selected some cardiovascular drugs. The list of medicinal agents selected in study along with their drug class and uses are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e (Tripathi KD, 2018; Recently marketed, 2021).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eList of selected Cardiovascular agents used in the current study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSr. No.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDrug name\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClass\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSub-Class\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUses\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlyceryl trinitrite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-anginal agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVasodilators\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAngina pectoris.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePropranolol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-anginal agent\u003c/p\u003e \u003cp\u003eAnti-arrhythmic agent\u003c/p\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eβ- adrenergic blockers\u003c/p\u003e \u003cp\u003eClass-II anti-adrenergic agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAngina pectoris, arrhythmia and hypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVerapamil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-anginal agent\u003c/p\u003e \u003cp\u003eAnti-arrhythmic agent\u003c/p\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalcium\u003c/p\u003e \u003cp\u003echannel blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAngina pectoris, arrhythmia and hypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiltiazem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-anginal agent\u003c/p\u003e \u003cp\u003eAnti-arrhythmic agent\u003c/p\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCalcium\u003c/p\u003e \u003cp\u003echannel blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAngina pectoris, arrhythmia and hypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNicorandil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-anginal agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePotassium\u003c/p\u003e \u003cp\u003echannel openers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChest pain caused by angina.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTrimetazidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-anginal agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnti-ischemic(anti-anginal) metabolic agent of the fatty acid oxidation inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAngina (chest pain).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuinidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-arrhythmic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClass-I agents membrane stabilizing agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eArrhythmia.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDisopyramide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-arrhythmic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClass-I membrane stabilizing agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eArrhythmia.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmiodarone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-arrhythmic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClass III agents widening action potential\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVentricular arrhythmias and atrial fibrillation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDofetilide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-arrhythmic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClass III agents widening action potential\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIrregular heartbeat (including atrial fibrillation or atrial flutter).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChlorthalidone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThiazide diuretics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigh blood pressure and fluid retention caused by various conditions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFurosemide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh ceiling diuretics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigh blood pressure, heart failure and oedema.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpironolactone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAldosterone antagonist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHyperaldosteronism caused by various conditions, including liver, heart or kidney disease.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndapamide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eThiazide diuretics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCaptopril\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eACE inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUsed alone or in combination with other medications to treat high blood pressure and heart failure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLosartan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAngiotensin (AT\u003csub\u003e1\u003c/sub\u003e) receptor blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHigh blood pressure and heart failure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAliskiren\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDirect renin inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUsed alone or in combination with some medications to treat high blood pressure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrazosin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eα- adrenergic blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUsed alone or in combination with other medications to treat high blood pressure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClonidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCentral sympatholytic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydralazine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eArteriolar\u003c/p\u003e \u003cp\u003eDilator\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLovastatin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hyperlipidemic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUsed together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePravastatin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hyperlipidemic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUsed to lower cholesterol levels.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBezfibrate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hyperlipidemic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoprotein lipase activators peroxisome proliferator-activated receptors alpha (PPARα agonists: Fibrates)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHyperlipidemia.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNicotinic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hyperlipidemic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipolysis and triglyceride\u003c/p\u003e \u003cp\u003esynthesis inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNiacin deficiency (pellagra).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEzetimibe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-hyperlipidemic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSterol absorption inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUsed together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of cholesterol\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePentoxifylline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHemorrheologic agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRheological agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces leg pain caused by poor blood circulation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCyclandelate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVasodilators\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVasodilators\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVarious blood vessel diseases, arteriosclerosis.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCilostazol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlatelet-aggregation inhibitors.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePhosphodisterase-3 inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces the symptoms of intermittent claudication.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eClopidogrel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlatelet-aggregation inhibitors.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAntiplatelet drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePrevents platelets from sticking together and forming blood clot.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDigoxin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDigitalis glycosides.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCardiac glycosides\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eArrhythmia and atrial fibrillation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDigitoxin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCardiac glycosides.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCardiac glycosides\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHeart failure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDopamine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInotropic agents.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSympatho-mimetics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSymptoms of low blood pressure, low cardiac output and improves blood flow to the kidneys.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVerquvo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDrugs for chronic heart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSoluble guanylate cyclase activator\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChronic heart failure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOrladeyo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-anginal agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlasma kallikrein inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHereditary angioedema.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVyndaquel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTTR stabilizing agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eprotein transthyretin receptor (TTR) stabilizer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCardiomyopathy caused by transthyretin mediated amyloidosis (ATTR-CM) in adults.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYupelri\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-cholinergic agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnti-cholinergics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChronic obstructive pulmonary disease (COPD).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGiapreza\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVasoconstrictor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSynthetic vasoconstrictor peptide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIncreases blood pressure in adults with septic or other distributive shock.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRhopressa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOcular anti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRHO kinase enzyme inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGlaucoma (ocular hypertension)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVyzulta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOcular anti-hypertensive agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProstaglandin\u003c/p\u003e \u003cp\u003eF-receptor agonist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOpen-angle glaucoma (ocular hypertension).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUptravi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-thrombic agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelective non-proteinoid IP prostacyclin receptor agonists.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePulmonary arterial hypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKengreal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-thrombic agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003csub\u003e2\u003c/sub\u003eY\u003csub\u003e12\u003c/sub\u003e purinoreceptor antagonist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePrevents the formation of harmful blood clots in the coronary arteries for adult patients undergoing percutaneous coronary intervention\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCorlanor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eInhibiting cardiac pacemaker current (I\u003csub\u003ef\u003c/sub\u003e) inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHyperpolarization-activated cyclic nucleotide-gated (HCN) channel blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces hospitalization from worsening heart failure.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSavaysa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDirect factor Xa inhibiting agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelective inhibitor of factor Xa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces the risk of stroke due to systemic embolism in patients with atrial fibrillation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLumason\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eImage enhancing agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eInert image enhancing agent and has no pharmacologic effect.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFor patients whose ultrasound image of the heart (echocardiograms) is hard to detect with ultrasound waves.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZontivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(PAR-1) antagonist.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProtease-activated receptor-1 (PAR-1) antagonists.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces the risk of heart attacks and stroke in high-risk patients.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOpsumit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEndothelin receptor antagonists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEndothelin receptor antagonists.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePulmonary arterial hypertension (PAH) in adults.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdempas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSoluble guanylate cyclase (sGC) stimulators\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSoluble guanylate cyclase (sGC) stimulators\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePulmonary hypertension.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEliquis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFactor Xa inhibiting agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eIndirect inhibitor of platelet aggregation induced by thrombin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces the risk of stroke and systemic embolism in patients with atrial fibrillation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJuxtapid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMicrosomal triglyceride transfer protein (MTP) inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCholesterol-lowering medications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces low-density lipoprotein (LDL) cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBelviq\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCNS stimulants\u003c/p\u003e \u003cp\u003eAnorexiants\u003c/p\u003e \u003cp\u003e5-HT\u003csub\u003e2\u003c/sub\u003eC receptor agonists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5-HT\u003csub\u003e2\u003c/sub\u003eC receptor activator\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChronic weight management.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZioptan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAnti-glucomic agent\u003c/p\u003e \u003cp\u003eProstaglandin agonists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelective agonist prostaglandin\u003c/p\u003e \u003cp\u003eF-receptor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFirazyr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBradykinin B2 receptor antagonists\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBradykinin B2 receptor antagonist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHereditary angioedema (HAE) acute attacks in people aged 18 years and older.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrilinta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOral anti-platelet agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDirect-acting P2Y12-receptor antagonist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces cardiovascular death and heart attack in patients with acute coronary syndromes (ACS).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eXarelto\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFactor Xa inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFactor Xa inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReduces the risk of blood clots, deep vein thrombosis (DVT), and pulmonary embolism (PE) following knee or hip replacement surgery.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEdarbi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAngiotensin II blocker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSelective AT\u003csub\u003e1\u003c/sub\u003e subtype angiotensin II receptor antagonist.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHypertension in adults.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFrom the therapeutic substances belonging to the class of CVS, we have identified a number of pharmaceuticals for the current research project. The reference books and research articles provide us the in-depth information regarding cardiovascular agents that is presented below.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Methodology","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Evaluation of the drug-likeness of selected phytoconstituents\u003c/h2\u003e \u003cp\u003eDrug likeness studies were conducted by utilizing Molsoft server by Navigating to \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://molsoft.com/mprop/\u003c/span\u003e\u003cspan address=\"https://molsoft.com/mprop/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e in Google or Chrome. It will redirect you to Molsoft. Which will give the drug likeness profile of drug molecules with the following information. Molecular Formula of the compound, Weight of Molecule, Number of hydrogen bond acceptors, Number of hydrogen bond donors, Log P, Polar surface area of a molecule (PSA), Drug Likeness Score.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Determination of pharmacokinetics of selected phytoconstituents\u003c/h2\u003e \u003cp\u003eADME studies are carried out using Schrodinger\u0026rsquo;s software vi a Maestro 12.4 interface. Various parameters were determined with the help of Schrodinger\u0026rsquo;s software (QikProp, 2021).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Determination of BBB and GI permeability of selected medicinal agents via BOILED-Egg model\u003c/h2\u003e \u003cp\u003eFor the prediction of the permeability of the selected CVS agents through the BBB and passive absorption of the drugs via GI tract the BOILED-Egg model from Swiss ADME database was utilized.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Results And Discussion","content":"\u003cdiv class=\"Section2\" id=\"Sec10\"\u003e\n \u003ch2\u003e4.1 Determination of physiochemical properties and drug likeness of selected medicinal agents\u003c/h2\u003e\n \u003cp\u003eA qualitative concept of drug likeness is used in drug design to assess what a \u0026quot;druglike\u0026quot; compound is in terms of factors such as bioavailability. In this study, various drug likeness parameters of the conventional and recently marketed bioactive drugs were calculated in order to understand the effect of physicochemical properties on bioavailability patterns in human body. The permissible ranges of physicochemical parameters for good oral bioavailability of drugs are\u003c/p\u003e\n \u003cdiv class=\"Section3\" id=\"Sec11\"\u003e\n \u003ch2\u003e4.1.1 \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eMW\u003c/span\u003e: Molecular weight of the drug should be lesser than (\u0026lt;\u0026thinsp;500 Daltons).\u003c/h2\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec12\"\u003e\n \u003ch2\u003e4.1.2 \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eHBA\u003c/span\u003e: Hydrogen Bond acceptors should be within ten (\u0026le;\u0026thinsp;10).\u003c/h2\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec13\"\u003e\n \u003ch2\u003e4.1.3 \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eHBD\u003c/span\u003e: Hydrogen Bond donors should be within five (\u0026le;\u0026thinsp;5).\u003c/h2\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec14\"\u003e\n \u003ch2\u003e4.1.4 \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eLog P\u003c/span\u003e: Partition coefficient of the drug (\u0026le;\u0026thinsp;5).\u003c/h2\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec15\"\u003e\n \u003ch2\u003e4.1.5 \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003ePSA\u003c/span\u003e: Polar surface area of the drug (90\u0026ndash;140\u0026Aring;).\u003c/h2\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec16\"\u003e\n \u003ch2\u003e4.1.6 \u003cspan class=\"BoldItalic\" name=\"Emphasis\" type=\"BoldItalic\"\u003eRO5\u003c/span\u003e: Rule of five violations (\u0026le;\u0026thinsp;1).\u003c/h2\u003e\n \u003cp\u003eMolsoft online server was used to screen the selected drugs\u0026rsquo; druggable characteristics. The results are displayed in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u0026nbsp;\u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe physicochemical properties and drug likeness data of selected CVS drugs\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSr. No\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDrug Name\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMW\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003e\u0026lt;\u0026thinsp;500)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHBA\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003e\u0026le;\u0026thinsp;10)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHBD\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003e\u0026le;\u0026thinsp;5)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLog P\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003e\u0026le;\u0026thinsp;5)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePSA\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e90\u0026ndash;140 (A\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRO5\u003c/p\u003e\n \u003cp\u003e(\u0026le;\u0026thinsp;1)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDrug likeness\u003c/p\u003e\n \u003cp\u003e(\u003cem\u003e\u0026gt;\u0026thinsp;0)\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlyceryl trinitrite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e179.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-1.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e114.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epropranolol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e259.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVerapamil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e454.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiltiazem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e414.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNicorandil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e211.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrimetazidine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e266.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuinidine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e324.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisopyramide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e339.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmiodarone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e645.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e32.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDofetilide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e441.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eO.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChlorthalidone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e257.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFurosemide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e330.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e96.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpironolactone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e416.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e47.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndapamide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e365.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e79.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaptopril\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e217.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLosartan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e422.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAliskiren\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e551.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e119.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrazosin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e383.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e81.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClonidine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e229.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHydralazine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e160.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e58.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLovastatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e404.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePravastatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e424.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e97.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBezfibrate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e361.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNicotinic acid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e123.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEzetimibe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e409.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePentoxifylline\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e278.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e57.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCyclandelate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e276.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCilostazol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e369.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e72.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClopidogrel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e321.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDigoxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e780.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e160.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDigitoxin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e764.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e144.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDopamine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e153.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003everquvo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e426.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e114.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOrladeyo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e562.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e85.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVyndaquel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e502.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e138.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYupelri\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e597.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e87.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGiapreza\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1045.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-4.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e328.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRhopressa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e453.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVyzulta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e507.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e116.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUptravi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e496.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e85.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKengreal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e774.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e198.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCorlanor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e468.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSavaysa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e541.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e113.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLumason\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e140.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZontivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e492.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOpsumit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e585.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e107.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdempas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e422.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e105.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEliquis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e459.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJuxtapid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e693.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e52.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBelviq\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e231.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZioptan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e452.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirazyr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1303.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-7.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e418.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBrilinta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e522.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e109.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eXarelto\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e435.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e75.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEdarbi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e568.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e117.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe results displayed in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e exhibit that maximum of the selected cardiovascular drugs possessed acceptable number of acceptors of hydrogen bonds (\u0026le;\u0026thinsp;10), hydrogen bond donors (\u0026le;\u0026thinsp;5), partition coefficients within recommended ranges (\u0026le;\u0026thinsp;5), and polar surface areas (90\u0026ndash;140\u0026Aring;) within permissible ranges. Few drugs do not comply with the given standard values for molecular weight of the drug (\u0026lt;\u0026thinsp;500 Daltons). Thus, the selected CVS drugs show good oral bioavailability as most of the drugs obeyed Lipinski\u0026rsquo;s rule of 5 (\u0026le;\u0026thinsp;1) and displayed drug likeness score above 0.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec17\"\u003e\n \u003ch2\u003e4.2 Determination of pharmacokinetic properties of selected medicinal agents\u003c/h2\u003e\n \u003cp\u003eThe purpose of ADME studies is to learn how well a substance (a drug compound) is processed by a human cell. In this study, numerous ADME parameters of the screened substances were determined in order to comprehend the impact of physicochemical and pharmacokinetic properties on bioavailability patterns in the human body, further all parameters of each of the selected CVS agents were subjected for the Heat-Map analysis and its represented in the Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eThe following parameters are included in this study:\u003c/p\u003e\n \u003cdiv class=\"Section3\" id=\"Sec18\"\u003e\n \u003ch2\u003e4.2.1 CNS (\u0026lt;\u0026thinsp;25 poor, \u0026gt;\u0026thinsp;500 great)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003ePredicted central nervous system activity on a -2 (inactive) to +\u0026thinsp;2 (active) scale. This parameter indicates the lipophilicity of the drugs, as non-lipophilic compounds do not normally traverse the cell wall membrane passively, whereas highly lipophilic molecules risk becoming stuck within the membranes.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec19\"\u003e\n \u003ch2\u003e4.2.2 Mol_MW (130.0 to 725.0 dalton)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter provides molecular weight of the molecule as lower MW\u0026thinsp;\u0026lt;\u0026thinsp;500D compound shows more aqueous solubility and higher MW\u0026thinsp;\u0026gt;\u0026thinsp;500D compound shows higher lipophilicity and high membrane permeability.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec20\"\u003e\n \u003ch2\u003e4.2.3 Dipole (1.0 to 12.5)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter provides the molecule\u0026apos;s calculated dipole moment, which is useful for determining the polarity of the chemical bond.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec21\"\u003e\n \u003ch2\u003e4.2.4 Volume (500.0 to 2000.0)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter serves details about the total accessible solvent volume in terms of cubic angstrom by utilizing a probe with a radius of 1.4 \u0026Aring;.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec22\"\u003e\n \u003ch2\u003e4.2.5 QplogPC16 (4.0 to 18.0)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter helps in predicting the distribution of drug in two immiscible phases i.e partition coefficient of hexadecane/gas.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec23\"\u003e\n \u003ch2\u003e4.2.6 QplogPoct (8.0 to 35.0)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe parameter QplogPoct aids to predict the distribution of drug in two immiscible phases i.e; octanol/gas partition coefficient.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec24\"\u003e\n \u003ch2\u003e4.2.7 QplogPw (4.0 to 45.0)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter assists in predicting the distribution of drug in two immiscible phases i.e; water/gas partition coefficient.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec25\"\u003e\n \u003ch2\u003e4.2.8 QplogPo/w (-2.0 to 6.5)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter indicates the distribution of drug in two immiscible phases i.e; partition coefficient of octanol/water.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec26\"\u003e\n \u003ch2\u003e4.2.9 \u003cstrong\u003eQplogS (-6.5 to 0.5)\u003c/strong\u003e\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eIt demonstrates the expected water solubility, where, S is the concentration of the solute which is in equilibrium with the crystalline solid\u0026rsquo;s saturated solution.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n \u003cdiv class=\"Section3\" id=\"Sec27\"\u003e\n \u003ch2\u003e4.2.10 CIQPlogS (-6.5 to 0.5)\u003c/h2\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eIt indicates the conformation-independent log S, wherein S in terms of mol dm\u003csup\u003e-3\u003c/sup\u003e is the concentration of the solute present in the saturated solution that is in equilibrium with the crystalline solid.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.11 QPlogHERG (Concentration below \u0026minus;\u0026thinsp;5)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter predicts the IC\u003csub\u003e50\u003c/sub\u003e value for blocking the human ether-a-go-go related genes (HERG) K\u003csup\u003e+\u003c/sup\u003e channels.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.12 QPPCaco (\u0026lt;\u0026thinsp;25 poor and \u0026gt;\u0026thinsp;500 great)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eIt\u0026rsquo;s the expected apparent Caco-2 cell permittivity in nanometer range per second. Caco-2 cells are a model for the gut-blood barrier and are an immortalised cell line of human colorectal adenocarcinoma cells. QikProp predictions are for passive transportation.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.13 QplogBB (Brain/blood partition coefficient predicted; -3.0 to 1.2)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eSince most of the drugs are taken orally, these values are CNS negative. For example, both serotonin and dopamine are CNS negative as they are too hydrophilic to pass the blood-brain barrier.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.14 QplogKp (-8.0 to 1.0)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThis parameter aids in estimating skin penetration (logKp) for transportation of the compound through mammalian epidermis.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.15 QPPMDCK (Predicted apparent Madin-Darby canine kidney; \u0026lt;25 poor and if, \u0026gt;\u0026thinsp;500 great)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eMDCK cell permeability is depicted in terms of nm/sec. MDCK cells are considered to be a good mimic for the BBB. QikProp predictions are for non-active transport.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.16 QplogKhsa (-1.5 to 1.5)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eBecause of the availability of more binding sites on HSA, this parameter aids in drug prediction. HSA is a bioavailable, agglomerated, and un-glycosylated monomeric protein that performs primarily as a transport protein for steroids, essential fats, and thyroid stimulating hormone, and plays an important role in extracellular fluid volume stabilization.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.17 %HOA (\u0026gt;\u0026thinsp;80% high, \u0026lt;\u0026thinsp;25% poor)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eOn a scale of 0 to 100%, human oral absorption was predicted. A quantifiable model of multiple linear regression is employed to make the prediction. Because they both measure the same property, this property usually correlates well with Human Oral Absorption.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.18 PSA (7.0-200.0 A\u003c/strong\u003e \u003csup\u003e\u0026nbsp;\u003cstrong\u003e2\u003c/strong\u003e\u0026nbsp;\u003c/sup\u003e \u003cstrong\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eThe surface sum of all polar atoms and molecules, predominantly oxygen and nitrogen, including their connected hydrogen atoms, is defined as the polar surface area. As a result, this parameter provides information about the Van-Der Waals total surface area of polar both nitrogen and oxygen atoms.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.19 RO5 (Maximum is 4 violations)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eLipinski\u0026rsquo;s rule of five RO5 has been separated into five parts. Those are: mol_MW\u0026thinsp;\u0026lt;\u0026thinsp;500, PSA 07-200 A\u003csup\u003e2\u003c/sup\u003e, donorHB\u0026thinsp;\u0026le;\u0026thinsp;5. accptHB\u0026thinsp;\u0026le;\u0026thinsp;10. Compounds that satisfy these rules are considered drug-like molecule. (The \u0026ldquo;five\u0026rdquo; refers to the limits, which are multiples of five.)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4.2.20 RO3 (Maximum number allowed is 3 violations)\u003c/strong\u003e\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eJorgensen\u0026rsquo;s rule of three RO3. The three rules are: QplogS should be \u0026gt;-5.7, QPPCaco should be \u0026gt;\u0026thinsp;22 nm/s, #Primary Metabolites should be \u0026lt;\u0026thinsp;7. Compounds that violate fewer rules (preferably no) of these regulations are much more probable to be orally convenient.\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003eThe colors blue, yellow, green, and red in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e of the heat-map analysis of the pharmacokinetic properties of selected CVS agents represent the lowest, moderate, highest, and extremely high values (corresponding to drugs that violated the particular rule), respectively. The results depicts that most of the selected CVS agents had good oral absorptivity as very few of the drugs violated Lipinski\u0026rsquo;s RO5 and Jorgensen\u0026rsquo;s RO3 and nearly all of the compounds showed 100% of human oral absorption. All the selected CVS drugs have displayed molecular weights, dipole moments, presumed partition coefficient of water/gas, lying between recommended ranges. It was found out that majority of the drugs displayed permissible values for certain parameters such as total solvent-accessible volume, predicted partition coefficient of hexadecane/gas, predicted partition coefficient of octanol/gas, predicted water solubility, aqueous solubility that is not dependent on conformation, predicted MDCK cells penetrability, predicted skin penetrability, the Vander Waal\u0026rsquo;s total surface area of polar atoms or molecules such as nitrogen and oxygen atoms and prediction of drug\u0026rsquo;s ability to bind to human serum albumin proteins. It was seen that only few drugs comply with the IC\u003csub\u003e50\u003c/sub\u003e values required for blocking of HERG K\u003csup\u003e+\u003c/sup\u003e channels and few drugs showed results lying between the recommended ranges for CNS activity. Thus, the results demonstrated that most of the selected CVS drugs had accountable values for all parameters of pharmacokinetic studies and are therefore regarded powerful drug candidates with great vascular permeability and bioavailability.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec28\"\u003e\n \u003ch2\u003e4.3 Determination of BBB and GI permeability of Selected medicinal agents via BOILED-Egg model\u003c/h2\u003e\n \u003cp\u003eAccording to the results displayed in the Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, few of the compounds that were found in the Egg-yolk were predicted to pass through the blood-brain barrier (BBB), and those drugs that were found in the Egg-white were predicted to be passively absorbed through the gastro-intestinal (GI) tract, whereas the drugs that are observed as a blue dot are predicted to be effluated from the central nervous system by p-glycoprotein, and drugs that are observed as a red dot were predicted to be not-effluated from central nervous system by p-glycoprotein.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThe physicochemical and pharmacokinetic properties of a number of chosen CVS agents were virtually assessed. A total of fifty-five bioactive components underwent screening for drug likeness, physiochemical properties and ADME parameters. There were twenty-three recently marketed medications and thirty-two conventional drugs in all. Based on the results, forty-six drugs obeyed Lipinski's RO5 and forty-five drugs obeyed Jorgensen\u0026rsquo;s RO3 wherein the physicochemical and pharmacokinetic parameters were within the recommended ranges. Around thirteen drugs were found in the Egg-yolk that were predicted to pass the BBB and twenty-five drugs found in the egg-white that were predicted to be passively absorbed through the GI tract. Therefore, the evaluated medicines reveal to be powerful drug candidates with strong membrane permeability and bioavailability. This study can be used for optimizing the marketed formulations and repurposing of the drugs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Principal and Vice Principal, KLE College of Pharmacy, Belagavi for providing us the research facilities and support for our research work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026ldquo;The authors declare no conflict of interest.\u0026rdquo;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026ldquo;This article contains Supplementary Material\u0026rdquo;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLima LM (2007) Modern medicinal chemistry. 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P.257 \u0026ndash; 80; 521\u0026ndash;604; 659 \u0026ndash; 94 (June 2018)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRecently marketed cardiovascular agents. Available via \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://wayback.archiveit.org/7993/20170111002417/http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/default.htm\u003c/span\u003e\u003cspan address=\"http://wayback.archiveit.org/7993/20170111002417/http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/default.htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, accessed03 June 2021\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQikProp Descriptors and Properties (2012) Update 2. Available via \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://gohom.win/ManualHom/Schrodinger/Schrodinger_2012_docs/general/qikprop_props.pdf\u003c/span\u003e\u003cspan address=\"http://gohom.win/ManualHom/Schrodinger/Schrodinger_2012_docs/general/qikprop_props.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e, accessed08 July 2021\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 3-4 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"CVS agents, Drug-likeness, physicochemical properties, pharmacokinetic parameters, Lipinski's RO5, Jorgensen’s RO3, BOILED-Egg","lastPublishedDoi":"10.21203/rs.3.rs-2653667/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2653667/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCardiovascular (CVS) drugs are medications whose primary effects are experienced by the heart and blood vessels to treat cardiovascular disorders such as coronary artery disease, arrhythmias, high blood-pressure, heart failure and stroke. Evaluation of drug-likeness is a qualitative research approach in drug design that examines the drug-like properties of any chemical compound used as a lead in terms of factors such as oral bioavailability. These ADME parameters can be used widely in drug discovery to optimize the properties needed to convert lead candidates into safe and effective drugs for human use. An approach to estimate the passive gastrointestinal (GI) absorption and blood-brain barrier (BBB) access of drugs is the BOILED-Egg model from Swiss-ADME. In the current study, we virtually screened fifty-five bioactive CVS agents, which twenty-three were newly marketed agents and thirty-two were conventional agents. PubChem database for canonical smile collection, Molsoft server for physicochemical properties and drug-likeness screening, Schrodinger's software for ADME parameters, Microsoft Excel software for Heat-Map analysis, Swiss-ADME database for construction of BOILED-Egg model were utilized. The study results revealed that out of fifty-five screened bioactive drugs, forty-six drugs obeyed Lipinski's rule of five (RO5) and forty-five drugs obeyed Jorgensen's rule of three (RO3), were within recommended ranges of physicochemical and pharmacokinetic properties. Few of the compounds found in the Egg-yolk and Egg-white were predicted to pass the BBB and GI, respectively. It can be concluded that maximum of the screened bioactive drugs are proved to be potent drug candidates with good membrane permeability and oral bioavailability.\u003c/p\u003e","manuscriptTitle":"Physicochemical and Pharmacokinetic Properties’ Screening of Selected Cardiovascular Agents: an in-silico Approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-09 23:57:39","doi":"10.21203/rs.3.rs-2653667/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ff10bfc0-d63f-4374-82ee-6170a56ce75a","owner":[],"postedDate":"March 9th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-10-20T02:29:12+00:00","versionOfRecord":[],"versionCreatedAt":"2023-03-09 23:57:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2653667","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2653667","identity":"rs-2653667","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}