{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T06:47:07Z","timestamp":1782456427251,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Discipline leader training program for the health system of Qingpu District of Shanghai","award":["XD2023-10"],"award-info":[{"award-number":["XD2023-10"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Cipepofol is a novel intravenous anesthetic whose pharmacokinetics (PK) may vary with dosing regimens, sampling sites, and physiological differences across populations. However, clinical PK data remain fragmented across study settings and are limited for special populations and individualized perioperative use, highlighting the need for a mechanistic modeling framework. This study aimed to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for cipepofol across diverse populations. Methods: Clinical data from nine studies were included, comprising 371 subjects and 3521 plasma concentration measurements. The model was established in healthy adults using HSK3486-101, qualified using healthy-adult data from HSK3486-111 and anesthesia induction datasets, and extrapolated to hepatic impairment, renal impairment, and elderly populations using pathophysiology-informed adjustments. Individualized external validation was further performed in adult and pediatric surgical patients using actual clinical dosing histories. Model performance was evaluated using concentration\u2013time profiles, goodness-of-fit plots, fold error, and geometric mean fold error (GMFE) for Cmax and AUC0\u2013t. Results: The model adequately described both arterial and venous plasma concentration\u2013time profiles across the establishment, qualification, extrapolation, and external validation datasets. Most predicted concentrations were within two-fold of the observed values, and the overall GMFE values were 1.22 for Cmax and 1.21 for AUC0\u2013t. Simulated exposure differences in hepatic impairment, renal impairment, and elderly subjects were generally limited, suggesting no clinically meaningful PK changes from a PK exposure perspective in these populations. The model also reproduced arterial\u2013venous concentration differences and supported the major contributions of UGT1A9 and CYP2B6 to cipepofol clearance. Conclusions: This PBPK model provides a mechanistic framework for characterizing cipepofol disposition and may inform future model-informed dosing studies.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060763","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Cipepofol Across Diverse Clinical Populations"],"prefix":"10.3390","volume":"18","author":[{"given":"Junmin","family":"Li","sequence":"first","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longjie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangbin","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixia","family":"Chen","sequence":"additional","affiliation":[{"name":"Haisco Pharmaceutical Group Co., Ltd., Chengdu 856000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyue","family":"Hu","sequence":"additional","affiliation":[{"name":"Haisco Pharmaceutical Group Co., Ltd., Chengdu 856000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8683-2603","authenticated-orcid":false,"given":"Xiaoqiang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmaceutical Sciences, Fudan University, Shanghai 201203, China"},{"name":"Quzhou Fudan Institute, Quzhou 324003, China"},{"name":"State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Tang","sequence":"additional","affiliation":[{"name":"Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7443226","DOI":"10.1155\/2023\/7443226","article-title":"Ciprofol: A Novel Alternative to Propofol in Clinical Intravenous Anesthesia?","volume":"2023","author":"Lu","year":"2023","journal-title":"Biomed. 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