Читать книгу Drug Transporters - Группа авторов - Страница 102

A recent physiologically based pharmacokinetic (PBPK) modeling study investigated drug–drug interactions using trimethoprim as an inhibitor of MATEs and cytochrome P450 2C8 [98]. The model included intestinal efflux by P‐glycoprotein, CYP3A4 metabolism, hepatic clearance, and renal clearance via filtration and secretion. The model predicted drug–drug and drug–drug–gene interactions between trimethoprim and several exogenous probe substrates (metformin, repaglinide, pioglitazone, and rifampicin). The predicted exposure (AUC) and Cmax ratios for substrates were within 1.5‐fold of the observed values in clinical studies. The study supported the enhanced usage of PBPK modeling to predict drug–drug interactions with transporters in lieu of conducting studies in healthy volunteers.