Organic cation transporters and their pharmacokinetic and pharmacodynamic consequences

Drug Metab Pharmacokinet. 2008;23(4):243-53. doi: 10.2133/dmpk.23.243.

Abstract

To clarify the considerable interindividual variability in the pharmacokinetics, efficacy, and toxicity of drugs, genetic polymorphism of drug transporters has attracted interest because these transporters play important roles in the gastrointestinal absorption, biliary and renal elimination, and distribution to target sites of their substrates. Of the over 325 members of the solute carrier superfamily, this review focuses on the molecular features, expressional regulation, and genetic polymorphisms of the organic cation transporter (OCT) family, and the pharmacokinetic or pharmacodynamic consequences for organic cationic drugs. Although the clinical significance is still unclear, many studies have reported the importance of OCTs in the tissue distribution and elimination of their substrates in vitro and in vivo, and the impact of functional non-synonymous single nucleotide polymorphisms or differential expression levels of OCTs on the large interindividual variation in the pharmacokinetics and response of organic cationic drugs such as metformin, imatinib, and cisplatin.

Publication types

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

MeSH terms

  • Animals
  • Benzamides
  • Cisplatin / toxicity
  • Humans
  • Imatinib Mesylate
  • Kidney / drug effects
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Metformin / pharmacokinetics
  • Metformin / pharmacology
  • Organic Cation Transport Proteins / chemistry
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / physiology*
  • Piperazines / therapeutic use
  • Polymorphism, Single Nucleotide
  • Pyrimidines / therapeutic use
  • Substrate Specificity

Substances

  • Benzamides
  • Organic Cation Transport Proteins
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Metformin
  • Cisplatin