Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of drug interaction

Expert Opin Drug Metab Toxicol. 2014 Mar;10(3):425-35. doi: 10.1517/17425255.2014.878703. Epub 2014 Jan 23.

Abstract

Introduction: Due to their multiple effects, glucocorticoids (GCs) have versatile medical uses. They can regulate many xenobiotic-metabolizing enzymes of the cytochrome P450 (CYP) superfamily, and thus, influence pharmacotherapy.

Areas covered: The aim of this paper is to summarize the molecular effects of GCs on CYP as well as the available clinical evidence on drug-drug interactions (DDIs) between GCs and other drugs in which GCs influence the metabolism of other medicines through modifying CYP activity. We used the factographic database DRUGDEX® along with bibliographic searches.

Expert opinion: Most of the literature reported CYP3A4 induction by GCs, but this was not proved in all research. As the conclusions on these DDIs are conflicting, there are several issues to be considered like the dosage of GCs, the length of GCs treatment and concomitant therapy, all of which can have an additive inducing effect. Further, in designing a DDI study, crossover studies are preferred. A literature search of the abovementioned information resources provided dissimilar results.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Drug Interactions
  • Gene Expression Regulation, Enzymologic*
  • Glucocorticoids / pharmacology*
  • Humans
  • Up-Regulation
  • Xenobiotics / pharmacology

Substances

  • Glucocorticoids
  • Xenobiotics
  • Dexamethasone
  • Cytochrome P-450 Enzyme System