Liang Xiaomin, Giacomini Kathleen M
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94158.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California 94158; Institute for Human Genetics, University of California, San Francisco, San Francisco, California 94158.
J Pharm Sci. 2017 Sep;106(9):2245-2250. doi: 10.1016/j.xphs.2017.04.078. Epub 2017 May 8.
Metformin, widely used as first-line treatment for type 2 diabetes, exists primarily as a hydrophilic cation at physiological pHs. As such, membrane transporters play a substantial role in its absorption, tissues distribution, and renal elimination. Multiple organic cation transporters are determinants of the pharmacokinetics of metformin, and many of them are important in its pharmacological action, as mediators of metformin entry into target tissues. Furthermore, a recent genome-wide association study in a large multi-ethnic population implicated polymorphisms in SLC2A2, encoding the glucose transporter, GLUT2, as important determinants of response to metformin. Here, we describe the key transporters associated with metformin pharmacokinetics and response.
二甲双胍作为2型糖尿病的一线治疗药物被广泛使用，在生理pH值下主要以亲水性阳离子形式存在。因此，膜转运蛋白在其吸收、组织分布和肾脏排泄中起着重要作用。多种有机阳离子转运蛋白是二甲双胍药代动力学的决定因素，其中许多在其药理作用中也很重要，作为二甲双胍进入靶组织的介质。此外，最近一项针对大型多民族人群的全基因组关联研究表明，编码葡萄糖转运蛋白GLUT2的SLC2A2基因多态性是二甲双胍反应的重要决定因素。在此，我们描述了与二甲双胍药代动力学和反应相关的关键转运蛋白。
