Reaction Phenotyping

Abstract

Reaction phenotyping is a process to identify enzymes responsible for the metabolism of a drug. It allows for the understanding of the role of metabolizing enzymes in drug elimination through quantifying the contribution of major enzymes to the total clearance of a drug. This is an important step in the prediction of pharmacokinetic and drug–drug interactions (DDI) of a new chemical entity (NCE). This chapter discusses the commonly used in vitro cytochrome P450 (P450) reaction phenotyping assays with highlights on key experimental conditions, main deliverables, and differentiation of each approach. The importance in the translation of in vitro reaction phenotyping data to in vivo is emphasized and highlighted through several published examples. Strategies in the application of CYP reaction phenotyping studies to support clinical pharmacokinetic and DDI assessment at different stages of drug discovery and development are also discussed and recommended.