Cellular and Molecular Neurobiology, Vol. 19, No. 3, 1999 Cytochrome P450 Enzymes and Drug Metabolism— Basic Concepts and Methods of Assessment Paul Glue 1,3 and Robert P. Clement 2 Received December 7, 1996; accepted February 20, 1997 SUMMARY 1. The cytochrome P450 enzyme family is one of the major drug metabolizing systems in man. 2. Factors such as age, gender, race, environment, and drug treatment may have considerable influence on the activity of these enzymes. 3. There are now well-established in vitro techniques for assessing the role of specific cytochrome P450 enzymes in the metabolism of drugs, as well as the inhibitory or inducing effects of drugs on enzyme activity. In vitro data have been utilized to predict clinical outcomes (i.e., pharmacokinetic interactions), with close correlations between in vitro and in vivo data. 4. This information can be of considerable practical assistance to clinicians, to help with rational prescribing or to prevent or minimize the potential for drug interactions. KEY WORDS: cytochrome P450; enzyme inhibition; enzyme induction; pharmacokinetics; drug interaction; in vitro assessment; clinical assessment. INTRODUCTION The purpose of this review is to introduce some basic concepts about the cytochrome P450 (CYP450) family of enzymes, with emphasis on in vitro and clinical methods of assessing enzyme activity. In addition to providing information on the metabolism and disposition of compounds, of more practical relevance is the possibility of predicting and managing drug : drug interactions and explaining individual differ- ences in response to or tolerability of prescribed drugs. In general terms, drug metabolizing reactions can be divided into two broad groups—Phase 1 reactions, which involve chemical alteration of drug structure (e.g., by oxidation, reduction or hydrolysis); and Phase 2 reactions, in which the drug molecule is conjugated (e.g., by glucuronidation, sulphation, acetylation, etc.). The best-researched enzyme family, and the most important (based on the propor- 1 Department of Clinical Pharmacology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033. 2 Department of Drug Metabolism, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033. 3 To whom correspondence should be addressed. 309 0272-4340/99/0600–0309$16.00/0  1999 Plenum Publishing Corporation