Metabolism-based drug-drug interactions: what determines individual variability in cytochrome P450 induction?

Tang C1, Lin JH, Lu AY
Source: Drug Metabolism and Disposition
Publication Date: (2005)
Issue: 33(5): 603-613
Cells used in publication:
Hepatocyte, mouse
Species: mouse
Tissue Origin: liver
Hepatocyte, rat
Species: rat
Tissue Origin: liver
Hepatocyte, human
Species: human
Tissue Origin: liver
Hepatocyte, Cynomolgus
Species: monkey
Tissue Origin: liver
Hepatocyte, Rhesus
Species: monkey
Tissue Origin: liver
Hepatocyte, canine
Species: canine
Tissue Origin:
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