二甲双胍的稳态药代动力学在健康志愿者中与有机阳离子转运体1（OCT1）基因型无关。
Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers.
作者信息
Christensen Mette Marie Hougaard, Højlund Kurt, Hother-Nielsen Ole, Stage Tore Bjerregaard, Damkier Per, Beck-Nielsen Henning, Brøsen Kim
机构信息
Department of Public Health, Clinical Pharmacology, University of Southern Denmark, J.B. Winsloews Vej 19, 5000, Odense, Denmark.
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
出版信息
Eur J Clin Pharmacol. 2015 Jun;71(6):691-697. doi: 10.1007/s00228-015-1853-8. Epub 2015 May 5.
PURPOSE
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.
目的
本研究旨在确定在有机阳离子转运体1基因（OCT1）中具有不同数量功能降低等位基因的健康志愿者体内二甲双胍的稳态药代动力学。
方法
该研究作为随机交叉试验的一部分进行。纳入了34名已知OCT1基因型的健康志愿者（12名具有两个野生型等位基因，13名具有一个，9名具有两个功能降低等位基因）。在其中一个研究阶段，他们每天两次服用1 g二甲双胍滴定至稳态。
结果
OCT1中功能降低等位基因的数量（0、1或2）对AUC(0 - 12)、C(max)或肾清除率（Cl(renal)）均无统计学显著影响：（AUC(0 - 12)：0、1、2分别为14、13和14 h ng/L（P = 0.61））；（C(max)：0、1、2分别为2192、1934和2233 ng/mL，（P = 0.26））以及（Cl(renal)：0、1、2分别为31、28和30 L/h（P = 0.57））。结论：在一组健康志愿者中，我们发现不同的OCT1基因型对二甲双胍稳态药代动力学没有影响。
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