Population Pharmacokinetics of a single bolus of Ciprofol in Chinese pediatric patients

Population Pharmacokinetics of a single bolus of Ciprofol in Chinese pediatric patients | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 18 February 2025 V1 Latest version Share on Population Pharmacokinetics of a single bolus of Ciprofol in Chinese pediatric patients Authors : Sicong Wang 0000-0001-9515-0201 , Yan Li , Zhiyan Hu , Longzhi Du , Ying Wang , Xiaoya Jiang , Lujin Li , and Wangning Shangguan [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.173986068.89466621/v1 Published BMC Anesthesiology Version of record Peer review timeline 241 views 175 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Aims: The study aimed to elucidate the population pharmacokinetics of ciprofol in surgical pediatric patients and to establish a validated dosing regimen for this demographic. Methods: In this study, 27 healthy Chinese children aged 1 to 9, scheduled for elective urologic surgery, received a 0.6 mg/kg bolus of ciprofol over 30 seconds. Thirteen arterial blood samples were collected from each child for analysis. A population pharmacokinetic analysis using nonlinear mixed-effects modeling was conducted with intensive sampling data, and safety assessments were performed throughout the trial. Results: Ciprofol’s pharmacokinetics were best described by a three-compartment model, with key parameters estimated as follows: clearance (CL) at 0.0313 L/min/kg, central compartment volume (V1) at 0.506 L/kg, and peripheral volumes V2 and V3 at 0.225 L/kg and 1.34 L/kg, respectively. Intercompartmental clearances were CL2 at 0.0278 L/min/kg and CL3 at 0.0199 L/min/kg. Including blood urea nitrogen (BUN) as a covariate for V1 improved the model statistically, but its effect on ciprofol exposure was minimal and not clinically significant. Age and weight had no impact on ciprofol’s pharmacokinetics. The study also reported that ciprofol was well-tolerated, with no hemodynamic adverse events. Conclusions: In pediatric patients, both CL and V1 of ciprofol are higher per kilogram than in adults, necessitating a higher induction dose. A 0.6 mg/kg dose in children aged 1 to 9 is expected to provide similar exposure without adverse effects. Population Pharmacokinetics of a Single Bolus of Ciprofol in Chinese pediatric patients Sicong Wang 1 , Yan Li 1 , Zhiyan Hu 1，2 , Longzhi Du 1 , Ying Wang 1 , Xiaoya Jiang 1 , Lujin Li 3 , Wangning Shangguan 1,2 1 Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China 2 Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang, China 3 Center for Drug Clinical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China Address correspondence to: Wangning Shangguan, No. 1111, East Section of Wenzhou Avenue, Wenzhou 325000, China Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Tel: +86-13587637891 Email: [email protected] A Principal Investigator statement The authors confirm that the Principal Investigator for this paper is Dr. Sicong Wang and that she had direct clinical responsibility for patients. Keywords Anesthesia, Children, Modelling and Simulation, Population analysis Word count: 4014 words Table count: 4 tables Figure count: 5 figures What is already known about this subject • Ciprofol (HSK3486) is a new intravenous anesthetic agent. • Anesthesia induced by ciprofol is characterized by improved hemodynamic stability and a marked reduction in pain. • The pharmacokinetic characteristics of ciprofol have been fully investigated in adult populations. What this study adds • The population pharmacokinetics in pediatric patients were described and predicted adequately. • Blood urea nitrogen significantly affected the central compartment’s volume of distribution for ciprofol, but simulations showed its impact on ciprofol exposure was minor and clinically insignificant. Weight and age did not influence ciprofol’s pharmacokinetics. • A 0.6mg/kg induction dose of ciprofol likely maintains comparable exposure without drug-related adverse events in pediatric patients. ABSTRACT Aims: The study aimed to elucidate the population pharmacokinetics of ciprofol in surgical pediatric patients and to establish a validated dosing regimen for this demographic. Methods: In this study, 25 healthy Chinese children aged 1 to 9, scheduled for elective urologic surgery, received a 0.6 mg/kg bolus of ciprofol over 30 seconds. Thirteen arterial blood samples were collected from each child for analysis. A population pharmacokinetic analysis using nonlinear mixed-effects modeling was conducted with intensive sampling data, and safety assessments were performed throughout the trial. Results: Ciprofol’s pharmacokinetics were best described by a three-compartment model, with key parameters estimated as follows: clearance (CL) at 0.0313 L/min/kg, central compartment volume (V 1 ) at 0.506 L/kg, and peripheral volumes V 2 and V 3 at 0.225 L/kg and 1.34 L/kg, respectively. Intercompartmental clearances were CL 2 at 0.0278 L/min/kg and CL 3 at 0.0199 L/min/kg. Including blood urea nitrogen (BUN) as a covariate for V 1 improved the model statistically, but its effect on ciprofol exposure was minimal and not clinically significant. Age and weight had no impact on ciprofol’s pharmacokinetics. The study also reported that ciprofol was well-tolerated, with no hemodynamic adverse events. Conclusions: In pediatric patients, both CL and V 1 of ciprofol are higher per kilogram than in adults, necessitating a higher induction dose. A 0.6 mg/kg dose in children aged 1 to 9 is expected to provide similar exposure without adverse effects. Supplementary Material File (bjcp-ciprofol.edited2.docx) Download 103.02 KB File (figure 1 flow chart of the study.doc) Download 24.00 KB File (figure 2.docx) Download 247.17 KB File (figure 3 goodness-of-fit plot of the final model.docx) Download 221.87 KB File (figure 4 visual predictive check plot of the final model.docx) Download 142.68 KB File (figure 5.docx) Download 22.56 KB Information & Authors Information Version history V1 Version 1 18 February 2025 Peer review timeline Published BMC Anesthesiology Version of Record 30 Jan 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords anaesthesia children critical care modelling and simulation paediatrics pharmacodynamics population analysis Authors Affiliations Sicong Wang 0000-0001-9515-0201 View all articles by this author Yan Li The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University View all articles by this author Zhiyan Hu View all articles by this author Longzhi Du The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University View all articles by this author Ying Wang The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University View all articles by this author Xiaoya Jiang The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University View all articles by this author Lujin Li Shanghai University of Traditional Chinese Medicine View all articles by this author Wangning Shangguan [email protected] The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University View all articles by this author Metrics & Citations Metrics Article Usage 241 views 175 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Sicong Wang, Yan Li, Zhiyan Hu, et al. Population Pharmacokinetics of a single bolus of Ciprofol in Chinese pediatric patients. Authorea . 18 February 2025. DOI: https://doi.org/10.22541/au.173986068.89466621/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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