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Effect of Genetic Variation in the Organic Cation Transporter 1, OCT1, on Metformin PharmacokineticsShu, Y; Brown, C; Castro, RA; Shi, RJ; Lin, ET; Owen, RP; Sheardown, SA; Yue, L; Burchard, EG; Brett, CM; Giacomini, KM
Clinical pharmacology and therapeutics, February 2008, Letnik: 83, Številka: 2Journal Article
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. Clinical Pharmacology & Therapeutics (2008) doi:10.1038/sj.clpt.6100275
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