ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1526266
This article is part of the Research TopicDrug Metabolism and Transport: The Frontier of Personalized Medicine Volume IIView all 20 articles
Population pharmacokinetic analysis of remimazolam after continuous infusion for sedation in critically ill patients
Provisionally accepted
Jingchun Chen1,2
Xipei Wang3Dong Chen2Junjiang Zhu3Kaiyi Peng4Ruizheng Tang4
Linhui Hu4Yirong Wang3
Yunpeng Bai1Lin Chang5
Chunbo Chen1*- 1Shenzhen People’s Hospital, Shenzhen, China
- 2South China University of Technology, Guangzhou, Guangdong Province, China
- 3Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China
- 4Maoming People's Hospital, Maoming, China
- 5Yichang Humanwell Pharmaceutical Co.Ltd, Yichang, China
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The aim of the present prospective study was to model the population pharmacokinetics of remimazolam after continuous infusion in critically ill patients, and to provide a guide for remimazolam administration based on simulations that were conducted.A total of 32 critically ill patients were enrolled in this study, with 236 plasma concentration data ultimately included for modeling. Plasma concentrations of remimazolam were quantified by a validated high-performance liquid chromatography-tandem mass spectrometry method, and the data were analyzed using non-linear mixed effect modeling. Concentration-time curves of remimazolam at different induction and maintenance doses were simulated and context-sensitive decrement times (CSDTs) were calculated using Monte Carlo simulations.A two-compartment model appropriately described the concentration-time profile of remimazolam in critically ill patients. The elimination clearance, volume of the central compartment, volume of the peripheral compartment, and peripheral compartmental clearance were estimated to be 58.2 L/h (95% CI, 47.8-72.3 L/h), 25.5 L (95% CI, 16.8-33.3 L), 34.5 L (95% CI, 26.0-58.8 L) and 21.9 L/h (95% CI, 12.2-34.6 L/h), respectively. No covariates significantly influenced the pharmacokinetic parameters of remimazolam. Internal validation proved the reliable predictive performance of the model. The CSDTs of remimazolam (10-90%) was independent of the infusion time.Remimazolam showed a predictable pharmacokinetic profile and was demonstrated to be suitable for long-term sedation in the intensive care unit, with dose adjustments only required dependent on the degree of the sedative effect.
Keywords: critically ill patients, population pharmacokinetics, Remimazolam, sedation, Context-sensitive decrement times
Received: 11 Nov 2024; Accepted: 25 Jun 2025.
Copyright: © 2025 Chen, Wang, Chen, Zhu, Peng, Tang, Hu, Wang, Bai, Chang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chunbo Chen, Shenzhen People’s Hospital, Shenzhen, China
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