Suraxavir marboxil (GP681) is an orally available prodrug that is converted in vivo to the active metabolite GP1707D07, a PA-targeting antiviral against influenza. Because GP1707D07 is primarily metabolized by CYP3A4, coadministration with CYP3A4 inhibitors could substantially alter the exposure of the active metabolite and therefore efficacy and safety.
To address this, we constructed and validated a mechanistic PBPK model that links the parent prodrug and its active metabolite and used it to predict DDIs with inhibitors of differing strengths. This study successfully constructed and verified the PBPK model of the prodrug GP681 and the active metabolite GP1707D07, and systematically simulated the interaction risk with CYP3A4 inhibitors of different intensities.
This model strategy provides an efficient and reliable methodological tool for the DDI evaluation of complex precursor drugs, and is expected to further guide the clinical development and safe medication practice of GP681.The work titled “Physiologically based pharmacokinetic (PBPK) modeling of drug–drug interactions between suraxavir marboxil and CYP3A4 inhibitors: Quantitative prediction of pharmacokinetic effects on active metabolite GP1707D07” was published in Pharmaceutical Science Advances (published on Oct. 2, 2025).
DOI: 10.1016/j.pscia.2025.100095