Role of organic cation transporters in drug-drug interaction

Expert Opin Drug Metab Toxicol. 2015;11(10):1619-33. doi: 10.1517/17425255.2015.1069274. Epub 2015 Jul 24.


Introduction: Organic cation transporters OCT1, OCT2 and OCT3 expressed in the small intestine, liver, brain and other organs play important roles in absorption, excretion and distribution of cationic drugs. Drug-drug interactions at OCTs may change pharmacokinetics, pharmacodynamics and drug toxicity. Knowledge about physiological and biomedical functions of OCTs and the molecular mechanisms of transport and inhibition is required to anticipate drug-drug interactions and their potential biomedical impact.

Areas covered: Current knowledge about structure, polyspecific cation binding and transport of OCTs is summarized. Tissue distributions of OCT1-3 and their presumed physiological roles in the small intestine, liver, kidney and brain are reported, and drugs that are transported by human OCT1-3 are listed. The impact of human OCTs for pharmacokinetics and pharmacodynamics of the antidiabetic metformin and antineoplastic platinum derivatives are discussed. In addition, interactions of drugs that are transported by OCTs observed in the kidney and liver are reported. Procedures to test novel drugs for drug-drug interactions at OCTs in vitro and in clinical studies are recommended.

Expert opinion: When performing in vitro testing for drug-drug interactions, it must be considered that one inhibitory drug may inhibit different transported drugs with different affinities. After positive in vitro testing for drug-drug interaction, clinical tests are obligatory.

Keywords: OCT1; OCT2; OCT3; SLC22 family of membrane transporters; drug–drug interaction; modeling of tertiary structure; organic cation transporters; polyspecific binding; transport mechanism; transported drugs.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Biological Transport
  • Drug Interactions*
  • Humans
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / pharmacology
  • Metformin / pharmacokinetics
  • Metformin / pharmacology
  • Organic Cation Transport Proteins / metabolism*
  • Organic Cation Transporter 1 / metabolism*
  • Organic Cation Transporter 2


  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 1
  • Organic Cation Transporter 2
  • SLC22A2 protein, human
  • solute carrier family 22 (organic cation transporter), member 3
  • Metformin