Roles of Rifampicin in Drug-Drug Interactions: Underlying Molecular Mechanisms Involving the Nuclear Pregnane X Receptor

Ann Clin Microbiol Antimicrob. 2006 Feb 15;5:3. doi: 10.1186/1476-0711-5-3.

Abstract

Rifampicin, an important drug in the treatment of tuberculosis, is used extensively despite its broad effects on drug-drug interactions, creating serious problems. The clinical importance of such interactions includes autoinduction leading to suboptimal or failed treatment. The concomitantly administered effects of rifampicin on other drugs can result in their altered metabolism or transportation that are metabolised by cytochromes P450 or transported by p-glycoprotein in the gastrointestinal tract and liver. This review paper summarises recent findings with emphases on the molecular mechanisms used to explain these broad drug-drug interactions. In general, rifampicin can act on a pattern: rifampicin activates the nuclear pregnane X receptor that in turn affects cytochromes P450, glucuronosyltransferases and p-glycoprotein activities. This pattern of action may explain many of the rifampicin inducing drug-drug interactions. However, effects through other mechanisms have also been reported and these make any explanation of such drug-drug interactions more complex.

Publication types

  • Review

MeSH terms

  • Antibiotics, Antitubercular / pharmacology*
  • Antibiotics, Antitubercular / therapeutic use
  • Cell Nucleus / drug effects
  • Cell Nucleus / physiology
  • Drug Interactions
  • Glucuronosyltransferase / drug effects
  • Glucuronosyltransferase / metabolism
  • Humans
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Steroid / drug effects
  • Receptors, Steroid / physiology*
  • Rifampin / pharmacology*
  • Tuberculosis / drug therapy

Substances

  • Antibiotics, Antitubercular
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Glucuronosyltransferase
  • Rifampin