Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers.
OBJECTIVE
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).


METHODS
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.


RESULTS
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)) CONCLUSIONS: In a cohort of healthy volunteers, we found no impact of different OCT1 genotypes on metformin steady-state pharmacokinetics.
Department of Public Health, Clinical Pharmacology, University of Southern Denmark, J.B. Winsloews Vej 19, 5000, Odense, Denmark. mmchristensen@health.sdu.dk.
Mette Marie Hougaard
MMH
Christensen
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Kurt
K
Højlund
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Ole
O
Hother-Nielsen
Department of Public Health, Clinical Pharmacology, University of Southern Denmark, J.B. Winsloews Vej 19, 5000, Odense, Denmark.
Tore Bjerregaard
TB
Stage
Department of Public Health, Clinical Pharmacology, University of Southern Denmark, J.B. Winsloews Vej 19, 5000, Odense, Denmark.|Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
Per
P
Damkier
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Henning
H
Beck-Nielsen
Department of Public Health, Clinical Pharmacology, University of Southern Denmark, J.B. Winsloews Vej 19, 5000, Odense, Denmark.
Kim
K
Brøsen
D000328:Adult; D000483:Alleles; D018592:Cross-Over Studies; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D055815:Young Adult
D007004:Hypoglycemic Agents; D027702:Organic Cation Transporter 1; D008687:Metformin