Heterozygous variants of multidrug and toxin extrusions(MATE1 and MATE2-K) have little influence on the disposition of metformin in diabetic patients
Heterozygous variants of multidrug and toxin extrusions(MATE1 and MATE2-K) have little influence on the disposition of metformin in diabetic patients
复制标题
多药和毒素挤出的杂合变异体（MATE1和MATE2-K）对糖尿病患者二甲双胍的处置影响不大
DOI：
10.1097/fpc.0b013e328335639f
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Inui K
中科院分区：
文献类型：
--
作者：
Toyama K;Yonezawa A;Tsuda M;Masuda S;Yano I;Terada T;Osawa R;Katsura T;Hosokawa M;Fujimoto S;Inagaki N;Inui K
多药和毒素挤出物（MATE 1/SLC 47 A1和MATE 2-K/SLC 47 A2）在二甲双胍的肾脏排泄中发挥重要作用。我们以前已经确定了非同义的MATE变体在低等位基因频率的功能缺陷。本研究的目的是评价杂合MATE变体对小鼠和人体二甲双胍分布的影响。Mate 1（±）杂合子小鼠中二甲双胍的药代动力学参数与Mate 1（+/+）野生型小鼠相当。在48例日本糖尿病患者中，7例患者携带杂合MATE变异体，无患者携带纯合MATE变异体。在有或没有杂合子MATE变异体的情况下，二甲双胍的口服清除率无显著差异。此外，通过使用非线性混合效应建模程序进行统计分析，肌酐清除率显著改善二甲双胍清除率的模型拟合，但杂合子MATE变体无此作用。总之，杂合子MATE变异体不会影响二甲双胍在糖尿病患者中的分布。
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.