The Hill-Langmuir Equation Governs Average Steady State of Target Occupancy for Pulsed Drug Delivery

The Hill-Langmuir Equation Governs Average Steady State of Target Occupancy for Pulsed Drug Delivery | 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 The Hill-Langmuir Equation Governs Average Steady State of Target Occupancy for Pulsed Drug Delivery Xiaomin Shi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4616065/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 Receptor occupancy is an important indicator for drug efficacy. Traditional pharmacodynamic model is constrained by assumption of rapid equilibrium, so it cannot provide a complete picture of drug action. Pulsed drug delivery is not aimed at the stability of the drug, but at accurately determining the time of dosing based on rhythm of onset. Using a minimal model, I found that the Hill-Langmuir equation which removes above assumption, can integrate pharmacokinetics and pharmacodynamics and can describe receptor occupancy under multiple dose regimens and pulsed drug delivery. This equation provides an optimization strategy for improving drug efficacy. For the traditional multiple dose regimen, we can optimize the elimination rate constant, association rate constant and drug-target residence time; however, for pulsed drug delivery, we can only optimize the drug-target residence time. Furthermore, using the dissociation rate constant, we are not only able to regulate binding affinity, but also control the stability of drug-target binding. And I provided two conditions must be followed in pulsed drug delivery design. These two conditions are the cost in reducing the stability of drug concentration. These results may reduce the failure rate of drug discovery. Hill-Langmuir equation average steady state drug-target residence time receptor occupancy binding kinetics Full Text Additional Declarations No competing interests reported. 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. We do this by developing innovative software and high quality services for the global research community. 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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-4616065","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":324116994,"identity":"f2ed709b-9315-4ec8-af42-07181ae53598","order_by":0,"name":"Xiaomin Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYDACCcYGBgYDGwY2IPvAhwqitRSkgbQwHpxxhigtIOLDYRDJfJi3hQgd8rOb26RuGJxP7JNuYDjA28Agzy92AL8WgzsHm41zDG4ntskcYDgguYPBcObsBAJaJBIbHwO1GLNJJDAcMDzDkGBwm4AW+RmJDYdzDM5BtCS2EaGF4QbYlgNyYC0HidFicCMR5JdkOTaZgw0HG85IEPaL/Iz0Z9I5f+x4gEF3+POfCht5fmlCDoMDcJxCooloLaQoHgWjYBSMghEFAM3jRQ496fIyAAAAAElFTkSuQmCC","orcid":"","institution":"Shanghai University","correspondingAuthor":true,"prefix":"","firstName":"Xiaomin","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2024-06-21 08:41:22","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4616065/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4616065/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":68510114,"identity":"7eaf58e1-724c-46ec-a548-240d36a94e4f","added_by":"auto","created_at":"2024-11-08 05:32:06","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":358380,"visible":true,"origin":"","legend":"","description":"","filename":"manuscriptSRR515.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4616065/v1_covered_4bd57c40-d66e-4779-b654-85fdb97f8ad4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Hill-Langmuir Equation Governs Average Steady State of Target Occupancy for Pulsed Drug Delivery","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"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":"Hill-Langmuir equation, average steady state, drug-target residence time, receptor occupancy, binding kinetics","lastPublishedDoi":"10.21203/rs.3.rs-4616065/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4616065/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eReceptor occupancy is an important indicator for drug efficacy. 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