Pharmacokinetics of CYP2C19- and CYP3A4-Metabolized Drugs in Cirrhosis Using a Whole-Body PBPK Approach.

ABSTRACT: Background/Objectives: Cirrhosis significantly alters physiological function and drug metabolism, particularly for medications primarily metabolized by CYP2C19 and CYP3A4. This study aims to establish a physiologically based pharmacokinetic (PBPK) modelling framework capable of predicting pharmacokinetic changes across different stages of cirrhosis, and to determine optimal dosing regimens that achieve drug exposure levels comparable to those in healthy individuals. Methods: We constructed a physiologically based pharmacokinetic (PBPK) model that incorporates six drugs, including omeprazole, lansoprazole, midazolam, ondansetron, verapamil, and alfentanil, which are metabolized primarily by CYP2C19 or CYP3A4. The pharmacokinetics of these drugs following oral or injectable adm

SUBMITTER: Mu R 

PROVIDER: S-EPMC12737180 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature