Genetic variants of the organic cation transporter 2 influence the disposition of metformin

Clin Pharmacol Ther. 2008 Nov;84(5):559-62. doi: 10.1038/clpt.2008.61. Epub 2008 Apr 9.

Abstract

Genetic variants of the organic cation transporter 2 (protein, OCT2; gene, SLC22A2) were evaluated for their contribution to the variations in the pharmacokinetics of metformin, especially to its renal elimination. Genetic variants of SLC22A2 (c.596C>T, c.602C>T, and c.808G>T) showed significant differences in metformin pharmacokinetics when compared with the reference genotype, with higher peak plasma concentration (C(max)) and area under the curve (AUC) and lower renal clearance (Cl(renal)), thereby suggesting that a decrease in transport function associated with the SLC22A2 variants results in reduced Cl(renal) of metformin and consequently leads to increased plasma concentrations.

Publication types

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

MeSH terms

  • Area Under Curve
  • Female
  • Genetic Variation
  • Humans
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Korea
  • Male
  • Metabolic Clearance Rate
  • Metformin / blood
  • Metformin / pharmacokinetics*
  • Organic Cation Transport Proteins / genetics*
  • Organic Cation Transporter 2

Substances

  • Hypoglycemic Agents
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • SLC22A2 protein, human
  • Metformin