Genetic Variants of the Organic Cation Transporter 2 Influence the Disposition of Metformin

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 Clrenal of metformin and consequently leads to increased plasma concentrations.