Application of PBPK Modeling in Predicting P-glycoprotein-Mediated Drug-Drug Interactions

P-glycoprotein (Pgp) plays a critical role for a variety of drugs in affecting the rate and extent of their absorption. Despite recently increased understanding of the role of Pgp in pharmacokinetics, it is still challenging to predict Pgp-mediated drug-drug interactions (Pgp-DDIs) in the intestine because knowledge gaps remain in establishing an in vitro-to-in vivo extrapolation (IVIVE) for Pgp kinetics of both substrates and inhibitors.
This talk will illustrate an application of physiologically-based pharmacokinetic (PBPK) modeling in predicting intestinal Pgp-DDIs covering:
• PBPK modeling strategy for Pgp-DDI prediction
• Rifampin-mediated Pgp induction
• Itraconazole- and verapamil-mediated Pgp inhibition
• IVIVE perspective for Pgp kinetics

Certara accelerates medicines to patients using proprietary biosimulation software and technology to transform traditional drug discovery and development. Its clients include 1,600 global biopharmaceutical companies, leading academic institutions, and key regulatory agencies across 60 countries.