Heterozygous variants of multidrug and toxin extrusions (MATE1 and MATE2-K) have little influence on the disposition of metformin in diabetic patients

Kana Toyama, Atsushi Yonezawa, Masahiro Tsuda, Satohiro Masuda, Ikuko Yano, Tomohiro Terada, Riyo Osawa, Toshiya Katsura, Masaya Hosokawa, Shimpei Fujimoto, Nobuya Inagaki, Ken Ichi Inui

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45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)135-138
Number of pages4
JournalPharmacogenetics and Genomics
Volume20
Issue number2
DOIs
Publication statusPublished - Feb 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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