Drug-drug Interaction Mediated by Inhibition and Induction of P-glycoprotein

Adv Drug Deliv Rev. 2003 Jan 21;55(1):53-81. doi: 10.1016/s0169-409x(02)00171-0.

Abstract

P-glycoprotein (P-gp), the most extensively studied ATP-binding cassette transporter, functions as a biological barrier by extruding toxic substances and xenobiotics out of cells. In vitro and in vivo studies have demonstrated that P-gp plays a significant role in drug absorption and disposition. Like cytochrome P450 enzymes, inhibition and induction of P-gp have been reported as the causes of drug-drug interactions. Because many prototypic inhibitors and inducers affect both CYP3A4 and P-gp, many drug interactions caused by these inhibitors and inducers involve these two systems. Clinically, it is very difficult to quantitatively differentiate P-gp-mediated drug interactions versus CYP3A4-mediated drug interactions, unless their relative contributions can be accurately estimated. Therefore, care should be exercised when interpreting drug interaction data and exploring the underlying mechanisms of drug interactions.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Blood-Brain Barrier / physiology
  • Clinical Trials as Topic
  • Drug Interactions*
  • Female
  • Humans
  • Intestinal Absorption
  • Pharmaceutical Preparations / metabolism
  • Pharmacokinetics
  • Placenta / metabolism
  • Placenta / physiology
  • Pregnancy
  • Tissue Distribution

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Pharmaceutical Preparations