A Mechanistic, Enantioselective, Physiologically Based Pharmacokinetic Model of Verapamil and Norverapamil, Built and Evaluated for Drug-Drug Interaction Studies.

ABSTRACT: The calcium channel blocker and antiarrhythmic agent verapamil is recommended by the FDA for drug-drug interaction (DDI) studies as a moderate clinical CYP3A4 index inhibitor and as a clinical Pgp inhibitor. The purpose of the presented work was to develop a mechanistic whole-body physiologically based pharmacokinetic (PBPK) model to investigate and predict DDIs with verapamil. The model was established in PK-Sim^®, using 45 clinical studies (dosing range 0.1-250 mg), including literature as well as unpublished Boehringer Ingelheim data. The verapamil R- and S-enantiomers and their main metabolites R- and S-norverapamil are represented in the model. The processes implemented to describe the pharmacokinetics of verapamil and norverapamil include enantioselective plasma protein bin

SUBMITTER: Hanke N 

PROVIDER: S-EPMC7355632 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature