期刊
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
卷 71, 期 6, 页码 691-697出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00228-015-1853-8
关键词
Metformin; OCT1; Reduced-function alleles; Pharmacogenetics; Healthy volunteers
资金
- Odense University Hospital Free Research Fund
- Danish Research Council for Health and Disease [0602-02695B]
The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1). The study was conducted as part of a randomized cross-over trial. Thirty-four healthy volunteers with known OCT1 genotypes (12 with two wild-type alleles, 13 with one and 9 with two reduced-function alleles) were included. In one of the study periods, they were titrated to steady-state with 1 g metformin twice daily. Neither AUC(0-12), C (max) nor Cl-renal were statistically significantly affected by the number of reduced-function alleles (0, 1 or 2) in OCT1: (AUC(0-12): 0, 1, 2: 14, 13 and 14 h ng/L (P= 0.61)); (C (max): 0, 1, 2: 2192, 1934 and 2233 ng/mL, (P = 0.26)) and (Cl-renal: 0, 1, 2: 31, 28 and 30 L/h (P = 0.57)) In a cohort of healthy volunteers, we found no impact of different OCT1 genotypes on metformin steady-state pharmacokinetics.
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