Prediction of drug-drug interaction relating to the induction of drug metabolizing enzymes

Abstract

Drug metabolizing enzymes are key molecules responsible for elimination of drug from the body. Inter- and intra-individual variability in activity of the drug metabolizing enzymes is a critical issue in clinical chemotherapy. Induction of drug metabolizing enzymes is regulated by ligand-activated transcription factors, i.e., nuclear receptors, and a cause of clinical drug-drug interaction. Concomitant use of inducers and victim drugs should be avoided in clinic depending on the degree of seriousness, while drug candidates that have enzyme inducing activity should be avoided in drug discovery and development. Therefore, prediction of these risks is strongly required. In this article, we discuss structure-activity relationship of interaction with nuclear receptors and in vitro-in vivo extrapolation of clinical drug-drug interactions.