Metabolism-based drug-drug interactions: what determines individual variability in cytochrome P450 induction?
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.
Tang
Cuyue
C
Department of Drug Metabolism, Merck Research Laboratories, Sumneytown Pike, West Point, PA 19486-0004, USA. cuyue_tang@merck.com
Lin
Jiunn H
JH
Lu
Anthony Y H
AY
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics*; D004347:Drug Interactions; D004790:Enzyme Induction / Q000502:physiology; D014644:Genetic Variation; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System