Population total and unbound pharmacokinetics and pharmacodynamics of ciprofol and M4 in subjects with various renal functions

Autor: Shuai‐bing Liu, Xia Yao, Jun Tao, Jian‐jun Yang, Ying‐ying Zhao, Dong‐wei Liu, Su‐yun Wang, Su‐ke Sun, Xu Wang, Pang‐ke Yan, Nan Wu, Xiao Liu, Xiao‐jian Zhang, Xin Tian, Zhang‐suo Liu
Rok vydání: 2022
Předmět:
Zdroj: British Journal of Clinical Pharmacology. 89:1139-1151
ISSN: 1365-2125
0306-5251
Popis: The aim of this study was to develop a population pharmacokinetic (PK) model to simultaneously describe both total and unbound concentrations of ciprofol and its major glucuronide metabolite, M4, and to link it to the population pharmacodynamics (PD) model in subjects with various renal functions.A total of 401 and 459 pairs of total and unbound plasma concentrations of ciprofol and M4, respectively, as well as 2190 bispectral index (BIS) data from 24 Chinese subjects with various renal functions were available. Covariates that may potentially contribute to the PK and PD variability of ciprofol were screened using a stepwise procedure. The optimal ciprofol induction dosing regimen was determined by model-based simulations.The PK of unbound ciprofol could best be described by a three-compartment model, while a two-compartment model could adequately describe unbound M4 PK. The concentrations of total and unbound ciprofol and M4 were linked using a linear protein binding model. The relationship between plasma concentrations of ciprofol and BIS data was best described by an inhibitory sigmoidal EThe developed model fully characterized the population PK and PD profiles of ciprofol. No dose adjustment is required in patients with mild and moderate renal impairment.
Databáze: OpenAIRE
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