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Drug Metabolism and Disposition Fast Forward
First published on January 26, 2005; DOI: 10.1124/dmd.104.003236

0090-9556/05/3305-603-613$20.00
DMD 33:603-613, 2005

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MINIREVIEW

METABOLISM-BASED DRUG-DRUG INTERACTIONS: WHAT DETERMINES INDIVIDUAL VARIABILITY IN CYTOCHROME P450 INDUCTION?

Cuyue Tang, Jiunn H. Lin, and Anthony Y. H. Lu

Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania (C.T., J.H.L.); and Department of Chemical Biology, College of Pharmacy, Rutgers University, Piscataway, New Jersey (A.Y.H.L.)

Individual variability in cytochrome P450 (P450) induction comprises an important component contributing to the difficulties in assessing and predicting metabolism-based drug-drug interactions in humans. In this article, we outline the major factors responsible for the individual variability in P450 induction, including variable transporter activity and metabolism of inducers in vivo, genetic variations of P450 genes and their regulatory regions, genetic variations of receptors and regulatory proteins required for induction, and different physiological and environmental elements. With a better understanding of the major determinants in P450 induction and a profile of the phenotypes of these determinants in each individual, it is believed that the individual variability in induction-mediated drug-drug interactions can be adequately evaluated.

Address correspondence to: Dr. Cuyue Tang, Department of Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, P.O. Box 4, WP75-100, West Point, PA 19486-0004. E-mail: cuyue_tang{at}merck.com




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