In vitro evidence for the role of OATP and OCT uptake transporters in drug-drug interactions

Expert Opin Drug Metab Toxicol. 2009 May;5(5):489-500. doi: 10.1517/17425250902911463.

Abstract

Background: Transport proteins, for example the drug export pump P-glycoprotein, are important for the absorption, distribution and excretion of drugs. Inhibition and induction of P-glycoprotein efflux function is a well-established mechanism of drug-drug interactions. Alteration of transporter-mediated drug uptake by concomitantly administered drugs may also result in a change in drug pharmacokinetics. These uptake transporter-mediated drug-drug interactions are the focus of this review.

Objective: To examine the current in vitro evidence on interactions mediated by OATPs (organic anion transporting polypeptides) and OCTs (organic cation transporters).

Methods: Comparing data of in vivo observed drug-drug interactions with in vitro analysed alterations in drug transport mediated by the hepatic expressed uptake transporters OATP1B1, OATP1B3 and OCT1 and by the renal expressed OCT2 protein.

Results/conclusions: Some of the previously in vivo described drug-drug interactions could be explained by alteration in uptake transporter function demonstrating that inhibition or induction of uptake transporters is a newly recognised mechanism of potential drug-drug interactions.

Publication types

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

MeSH terms

  • Biological Transport / physiology
  • Drug Interactions*
  • Humans
  • Liver / metabolism
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters / metabolism*
  • Organic Anion Transporters, Sodium-Independent / metabolism
  • Organic Cation Transport Proteins / metabolism*
  • Organic Cation Transporter 1 / metabolism
  • Organic Cation Transporter 2
  • Pharmaceutical Preparations / metabolism
  • Solute Carrier Organic Anion Transporter Family Member 1B3

Substances

  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 1
  • Organic Cation Transporter 2
  • Pharmaceutical Preparations
  • SLC22A2 protein, human
  • SLCO1B1 protein, human
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3