ABSTRACT

Determination of the potential effects of new molecules on the activities of drug metabolizing enzymes in vitro can be useful in several areas of drug research. The data can serve as an indicator of whether a new compound could cause pharmacokinetic-based drug-drug interactions. Among the many drug metabolizing enzymes that could be potentially inhibited by new drugs, the ones of greatest focus are the cytochrome P450s followed by the uridine diphosphate-glucuronosyltransferase enzymes. High quality in vitro inhibition data requires not only sound enzyme kinetic practice but also robust quantitative methods to analyze the incubation samples. CYP3A poses the greatest complexities when attempting to measure the potential effect of a new drug as an inhibitor. Collection of in vitro data on the ability of experimental drugs to inhibit drug metabolizing enzymes is important to drug development because the information is used both in the design of clinical drug-drug interaction studies and in determining enzymes requiring no further evaluation.