Prediction of transporter-mediated drug-drug interactions in the liver: Based on in vitro inhibition study and clearance concept

The liver mainly regulates the ADME (absorption, distribution, metabolism and excretion) properties of numerous endogenous and exogenous compounds with metabolic enzymes such as chytochrome P450 (CYP) and membrane transporters such as organic anion transporting polypeptides (OATPs) and organic cation transporters (OCTs). Recently, clinical studies investigating drug-drug interactions (DDIs) or pharmacogenetics (PGx) have revealed that, in addition to drug metabolizing enzymes, an alteration in the membrane transport activity can also affect the pharmacokinetics and subsequent pharmacodynamics/toxicological effect of their substrates (1). Thus, pharmaceutical companies are now trying to avoid or to predict these events in the early phase of drug development.