Physiologically-based pharmacokinetic modeling to predict CYP3A4-mediated drug-drug interactions of finerenone.

ABSTRACT: Finerenone is a nonsteroidal, selective mineralocorticoid receptor antagonist that recently demonstrated its efficacy to delay chronic kidney disease (CKD) progression and reduce cardiovascular events in patients with CKD and type 2 diabetes. Here, we report the development of a physiologically-based pharmacokinetic (PBPK) model for finerenone and its application as a victim drug of cytochrome P450 3A4 (CYP3A4)-mediated drug-drug interactions (DDIs) using the open-source PBPK platform PK-Sim, which has recently been qualified for this application purpose. First, the PBPK model for finerenone was developed using physicochemical, in vitro, and clinical (including mass balance) data. Subsequently, the finerenone model was validated regarding the contribution of CYP3A4 metabolism to total clea

SUBMITTER: Wendl T 

PROVIDER: S-EPMC8846632 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature