In Vitro CYP/FMO Reaction Phenotyping

Reaction phenotyping is the process of identifying in vitro the drug-metabolizing enzymes involved in the clearance of a drug in order to predict whether the drug might be susceptible to changes in its exposure or to cause changes in the exposure of concomitantly administered drugs. The semi-quantitative assessment of the relative contributions of these pathways can provide early insight to the potential for drug-drug interactions or to possible affinities to functionally polymorphic enzymes which can cause inter-subject variability in the clinic. This chapter presents an initial strategy that can be implemented at the drug discovery or early development stage of a drug candidate to evaluate the extent of in vitro clearance, identify possible metabolic liabilities and predict potential interaction with other relevant drugs.