Organic cation transporters and their roles in antiretroviral drug disposition

Expert Opin Drug Metab Toxicol. 2009 Jul;5(7):773-87. doi: 10.1517/17425250902997959.

Abstract

Background: Understanding metabolising processes and drug-transporter interactions is particularly crucial to the management of patients with HIV infection, given the several antiretroviral drugs that must be taken lifelong and the use of other medications for HIV-related and non-HIV-related conditions. Several interactions of antiretroviral drugs with metabolising enzymes, especially cytochrome P450 and ATP-dependent transporter P-glycoprotein, have been described but the role of the organic cation transporters (OCTs) is less clearly defined.

Objective: To review the relevance of the OCTs for antiretroviral drug disposition.

Methods: Interactions of OCTs with antiretroviral drugs and evidence for clinical relevance are discussed.

Results/conclusion: Several antiretroviral drugs show relevant interactions with the OCTs in cell-based experiments and the OCTs are highly upregulated in HIV-infected patients. For evaluating the clinical significance, interaction studies in HIV patients and reliable in vitro models for delineation of in vivo effects are needed.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Retroviral Agents / metabolism*
  • Humans
  • Organic Cation Transport Proteins / chemistry
  • Organic Cation Transport Proteins / physiology*
  • Organic Cation Transporter 1 / chemistry
  • Organic Cation Transporter 1 / physiology
  • Organic Cation Transporter 2
  • Tissue Distribution / physiology

Substances

  • Anti-Retroviral Agents
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 1
  • Organic Cation Transporter 2
  • SLC22A2 protein, human