High-performance PBPK model for predicting CYP3A4 induction-mediated drug interactions: a refined and validated approach.

ABSTRACT:

Introduction

The cytochrome P450 enzyme 3A4 (CYP3A4) mediates numerous drug-drug interactions (DDIs) by inducing the metabolism of co-administered drugs, which can result in reduced therapeutic efficacy or increased toxicity. This study developed and validated a Physiologically Based Pharmacokinetic (PBPK) model to predict CYP3A4 induction-mediated DDIs, focusing on the early stages of clinical drug development.

Methods

The PBPK model for rifampicin, a potent CYP3A4 inducer, was developed and validated using human pharmacokinetic data. Subsequently, PBPK models for 'victim' drugs were constructed and validated. The PBPK-DDI model's predictive performance was assessed by comparing predicted area under the curve (AUC) and maximum concentration (C_max) ratioswith empi

SUBMITTER: Yang CG 

PROVIDER: S-EPMC11897275 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature