Modelled plasma concentrations of pemafibrate with co-administered typical cytochrome P450 inhibitors clopidogrel, fluconazole, or clarithromycin predicted by physiologically based pharmacokinetic modelling in virtual populations.

Modelled plasma concentrations of pemafibrate with co-administered typical cytochrome P450 inhibitors clopidogrel, fluconazole, or clarithromycin predicted by physiologically based pharmacokinetic modelling in virtual populations. Xenobiotica. 2020 Jul 06;:1-23 Authors: Ogawa SI, Shimizu M, Yamazaki H Abstract Oral antidyslipidaemic drug pemafibrate is cleared from human plasma via hepatic uptake by organic anion transporting polypeptide (OATP) 1B1 and oxidation by cytochromes P450 (P450) 2C8, 2C9, and 3A4. The pharmacokinetic profiles of pemafibrate with virtual administrations of P450 inhibitors and/or disease interactions were generated using a physiologically based pharmacokinetic (PBPK) model previously established for co-administration of pemafibrate with OATP1B1 inhibitors.This PBPK model was validated in the current study using reported maximum pemafibrate plasma concentrations and areas under the curve from interaction studies in healthy subjects co-administered with clopidogrel (P450 2C8 inhibitor), fluconazole (P450 2C9/3A4 inhibitor), or clarithromycin (P450 3A4 inhibitor).Virtual co-administrations of pemafibrate with clopidogrel, fluconazole, or clarithromycin increased the predicted plasma exposures of pemafibrate 1.4-1.7-fold, 1.2-1.4-fold, and 2.9-11-fold, respectively, in subjects with or without moderate or severe renal impairment or Child-Pugh A or B liver cirrhosis. Some of the exposure-enhancing effects of clari...
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research