Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.

ABSTRACT: Vonoprazan is metabolized extensively through CYP3A and is an in vitro time-dependent inhibitor of CYP3A. A tiered approach was applied to understand the CYP3A victim and perpetrator drug-drug interaction (DDI) potential for vonoprazan. Mechanistic static modeling suggested vonoprazan is a potential clinically relevant CYP3A inhibitor. Thus, a clinical study was conducted to evaluate the impact of vonoprazan on the exposure of oral midazolam, an index substrate for CYP3A. A physiologically-based pharmacokinetic (PBPK) model for vonoprazan was also developed using in vitro data, drug- and system-specific parameters, and clinical data and observations from a [¹⁴ C] human absorption, distribution, metabolism, and excretion study. The PBPK model was refined and verified using data f

SUBMITTER: Mulford DJ 

PROVIDER: S-EPMC10088082 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature