Assessing Cytochrome P450 Drug Interaction Risk for Dordaviprone Using Physiologically Based Pharmacokinetic Modeling.

ABSTRACT: A physiologically based pharmacokinetic (PBPK) model was developed and verified for dordaviprone, a small molecule with antitumor effects in glioma patients. The model was applied to assess the drug-drug interaction (DDI) potential of dordaviprone as a victim of CYP3A4 inhibitors and inducers, and as a perpetrator of CYP3A4, CYP2C8, CYP2D6 inhibition. A combination of in vitro and clinical data was used to develop a minimal distribution PBPK model with a single adjusting compartment and mechanistic absorption using the Simcyp Population-Based Simulator (V21). Simulated maximum concentration (Cmax) and area under the concentration time curve (AUC) of the 3 clinical studies used to verify the PBPK model were within 1.4-fold of observed exposures. The simulated increase in dordaviprone AUC an

SUBMITTER: Jaiswal S 

PROVIDER: S-EPMC12521050 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature