In Vitro–In Vivo Extrapolation of Metabolism- and Transporter-Mediated Drug–Drug Interactions—Overview of Basic Prediction Methods

Evaluation of drug–drug interaction (DDI) risk is vital to establish benefit–risk profiles of investigational new drugs during drug development. In vitro experiments are routinely conducted as an important first step to assess metabolism- and transporter-mediated DDI potential of investigational new drugs. Results from these experiments are interpreted, often with the aid of in vitro–in vivo extrapolation methods, to determine whether and how DDI should be evaluated clinically to provide the basis for proper DDI management strategies, including dosing recommendations, alternative therapies, or contraindications under various DDI scenarios and in different patient population. This article provides an overview of currently available in vitro experimental systems and basic in vitro–in vivo extrapolation methodologies for metabolism- and transporter-mediated DDIs.