Physiologically based pharmacokinetic (PBPK) modeling of drug-drug interactions between suraxavir marboxil and CYP3A4 inhibitors: Quantitative prediction of pharmacokinetic effects on active metabolite GP1707D07.

ABSTRACT: Suraxavir marboxil (GP681) is a promising novel prodrug influenza polymerase acidic (PA) inhibitor whose active metabolite, suraxavir (GP1707D07), is primarily metabolized by cytochrome P450 3A4 (CYP3A4), raising concerns about drug-drug interactions (DDI) with CYP3A4 inhibitors. Traditional DDI assessment methods are limited for evaluating all potential combinations. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model to predict the DDI risk between GP681 and CYP3A4 inhibitors of varying potency. The model was developed based on physicochemical and in vitro parameters, as well as clinical data, including a phase I single ascending dose study of GP681 tablets and a single-center phase I study evaluating the DDI between GP681 and strong CYP3A4 inhibitor itracona

SUBMITTER: Yang L 

PROVIDER: S-EPMC12709922 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature