The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters

Trends Pharmacol Sci. 2010 Jan;31(1):22-35. doi: 10.1016/j.tips.2009.10.001. Epub 2009 Dec 11.

Abstract

Treatment of human immunodeficiency virus (HIV) infection involves a combination of several antiviral agents belonging to different pharmacological classes. This combination is referred to as highly active antiretroviral therapy (HAART). This treatment has proved to be very effective in suppressing HIV replication, but antiretroviral drugs have complex pharmacokinetic properties involving extensive drug metabolism and transport by membrane-associated drug carriers. Combination drug therapy often introduces complex drug-drug interactions that can result in toxic or sub-therapeutic drug concentrations, compromising treatment. This review focuses on the role of ATP-binding cassette (ABC) membrane-associated efflux transporters and solute carrier (SLC) uptake transporters in antiretroviral drug disposition, and identifies clinically important antiretroviral drug-drug interactions associated with changes in drug transport.

Publication types

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

MeSH terms

  • ATP-Binding Cassette Transporters / drug effects
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / pharmacology*
  • Antiretroviral Therapy, Highly Active / methods
  • Biological Transport / drug effects
  • Drug Interactions
  • HIV Infections / drug therapy*
  • Humans
  • Membrane Transport Proteins / drug effects*
  • Membrane Transport Proteins / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Anti-HIV Agents
  • Membrane Transport Proteins