Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics

Clin Pharmacol Ther. 2008 Feb;83(2):273-80. doi: 10.1038/sj.clpt.6100275. Epub 2007 Jul 4.


The goal of this study was to determine the effects of genetic variation in the organic cation transporter 1, OCT1, on the pharmacokinetics of the antidiabetic drug, metformin. Twenty healthy volunteers with known OCT1 genotype agreed to participate in the study. Each subject received two oral doses of metformin followed by collection of blood and urine samples. OCT1 genotypes had a significant (P<0.05) effect on metformin pharmacokinetics, with a higher area under the plasma concentration-time curve (AUC), higher maximal plasma concentration (Cmax), and lower oral volume of distribution (V/F) in the individuals carrying a reduced function OCT1 allele (R61C, G401S, 420del, or G465R). The effect of OCT1 on metformin pharmacokinetics in mice was less than in humans possibly reflecting species differences in hepatic expression level of the transporter. Our studies suggest that OCT1 genotype is a determinant of metformin pharmacokinetics.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Animals
  • Area Under Curve
  • Blood Glucose / drug effects
  • Catecholamine Plasma Membrane Transport Proteins / genetics*
  • Catecholamine Plasma Membrane Transport Proteins / metabolism
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / urine
  • Male
  • Metformin / administration & dosage
  • Metformin / blood
  • Metformin / pharmacokinetics*
  • Metformin / urine
  • Mice
  • Mice, Knockout
  • Octamer Transcription Factor-1 / genetics*
  • Octamer Transcription Factor-1 / metabolism
  • Phenotype
  • Polymorphism, Genetic*
  • Reference Values
  • Species Specificity


  • Blood Glucose
  • Catecholamine Plasma Membrane Transport Proteins
  • Hypoglycemic Agents
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Slc22a1 protein, mouse
  • Metformin