A physiologically based pharmacokinetic model of clopidogrel in populations of European and Japanese ancestry: An evaluation of CYP2C19 activity.

ABSTRACT: Treatment response to clopidogrel is associated with CYP2C19 activity through the formation of the active H4 metabolite. The aims of this study were to develop a physiologically based pharmacokinetic (PBPK) model of clopidogrel and its metabolites for populations of European ancestry, to predict the pharmacokinetics in the Japanese population by CYP2C19 phenotype, and to investigate the effect of clinical and demographic factors. A PBPK model was developed and verified to describe the two metabolic pathways of clopidogrel (H4 metabolite, acyl glucuronide metabolite) for a population of European ancestry using plasma data from published studies. Subsequently, model predictions in the Japanese population were evaluated. The effects of CYP2C19 activity, fluvoxamine coadministration (CYP2C19 i

SUBMITTER: Duong JK 

PROVIDER: S-EPMC8934724 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature