{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:20:36Z","timestamp":1771928436089,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Objective<\/jats:title>\n To develop and validate a population pharmacokinetic\/pharmacodynamic (PK\/PD) model for ciprofol in elderly surgical patients, delineating its pharmacokinetic profile and concentration-effect relationship to inform precision dosing.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Twenty patients (aged \u226565 years) undergoing elective surgery were enrolled. We performed population PK\/PD analysis using nonlinear mixed-effects modeling on 386 arterial blood samples and synchronized Bispectral Index (BIS) data. A linear three-compartment model and a sigmoid Emax model described the PK and PD (BIS), respectively. Covariates (age, weight, gender, and laboratory parameters) were tested via stepwise selection. Model performance was evaluated using goodness-of-fit plots, bootstrap (\n n<\/jats:italic>\n = 1,000), and prediction-corrected visual predictive checks. Dosing regimens were optimized via Monte Carlo simulation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A three-compartment model best described the PK. The center volume (V\n 1<\/jats:sub>\n ) was generally approximated at 2.95\u00a0L, but the peripheral volumes (V\n 2<\/jats:sub>\n and V\n 3<\/jats:sub>\n ) were 45.15\u00a0L and 76.79\u00a0L, respectively. The clearance (CL) was assessed at 1.01\u00a0L\u00a0min\n -1<\/jats:sup>\n . Body weight and age significantly influenced CL. PD analysis showed rapid effect-site equilibration (K\n e0<\/jats:sub>\n : 1.09\u00a0min\n -1<\/jats:sup>\n ), with an EC\n 50<\/jats:sub>\n of 233.91\u00a0ng\u00a0mL\n -1<\/jats:sup>\n and a Hill coefficient of 3.00. No covariates significantly affected PD parameters. The model exhibited sufficient fit and strong predictive efficacy. The simulation results confirmed that administering an intravenous loading dose of 0.4\u00a0mg\u00a0kg\n -1<\/jats:sup>\n over 1\u00a0min, followed by an initial continuous infusion at a rate of 0.6\u00a0mg\u00a0kg\n -1<\/jats:sup>\n \u00b7h\n -1<\/jats:sup>\n for 2\u00a0h, could stably maintain the patients\u2019 BIS values within the target range of 40\u201360.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n A population PK\/PD model for ciprofol in elderly patients was successfully established and validated. The model supports optimized, individualized dosing to achieve target anesthesia depth in this population.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphar.2026.1764590","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:32:33Z","timestamp":1770013953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From pharmacokinetics to precision dosing: optimizing continuous infusion regimens of ciprofol for elderly patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiaxi","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, General Hospital of Southern Theater Command of PLA","place":["Guangzhou, Guangdong, China"]},{"name":"The First School of Clinical Medicine, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"He","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, General Hospital of Southern Theater Command of PLA","place":["Guangzhou, Guangdong, China"]},{"name":"The First School of Clinical Medicine, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowen","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, General Hospital of Southern Theater Command of PLA","place":["Guangzhou, Guangdong, China"]},{"name":"The First School of Clinical Medicine, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, General Hospital of Southern Theater Command of PLA","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, General Hospital of Southern Theater Command of PLA","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, General Hospital of Southern Theater Command of PLA","place":["Guangzhou, Guangdong, China"]},{"name":"The First School of Clinical Medicine, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1016\/j.bja.2022.08.026","article-title":"Remifentanil pharmacodynamics during conscious sedation using algometry: a more clinically relevant pharmacodynamical model","volume":"129","author":"Abad-Torrent","year":"2022","journal-title":"Br. 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