期刊
PHARMACOGENETICS AND GENOMICS
卷 20, 期 2, 页码 135-138出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FPC.0b013e328335639f
关键词
creatinine clearance; H+/organic cation antiporter; metformin; organic cation transporter; pharmacokinetics
资金
- Ministry of Education, Science, Culture, and Sports of Japan
- Grants-in-Aid for Scientific Research [22390029, 21590156] Funding Source: KAKEN
Multidrug and toxin extrusions (MATE1/SLC47A1 and MATE2-K/SLC47A2) play important roles in the renal excretion of metformin. We have previously identified the nonsynonymous MATE variants with functional defects at low allelic frequencies. The purpose of this study was to evaluate the effects of heterozygous MATE variants on the disposition of metformin in mice and humans. Pharmacokinetic parameters of metformin in Mate1(+/-) heterozygous mice were comparable with those in Mate1(+/+) wild-type mice. Among 48 Japanese diabetic patients, seven patients carried heterozygous MATE variant and no patient carried homozygous MATE variant There was no significant difference in oral clearance of metformin with or without heterozygous MATE variants. In addition, creatinine clearance, but not heterozygous MATE variants, significantly improved the model fit of metformin clearance by statistical analysis using the nonlinear mixed-effects modeling program. In conclusion, heterozygous MATE variants could not influence the disposition of metformin in diabetic patients. Pharmacogenetics and Genomics 20:135-138 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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