Metformin transport by renal basolateral organic cation transporter hOCT2

Purpose. Metformin, an antihyperglycemic agent, is eliminated by tubular secretion in addition to glomerular filtration in the human kidney. This study was performed to characterize metformin transport by human organic cation transporter 2 (hOCT2), the most abundant organic cation transporter in the basolateral membranes of the human kidney. Methods. Accumulation of [C-14]metformin was assessed by the tracer experiments in the human embryonic kidney (HEK293) cells expressing hOCT2. Results. The transport of [C-14]metformin was markedly stimulated in hOCT2-expressing cells compared with the vector-transfected cells. The accumulation of [C-14]metformin was concentrative and was dependent on the membrane potential, showing consistency with the characteristics of hOCT2. The apparent K-m and V-max values of [C-14]metformin transport by hOCT2-expressing HEK293 cells were 1.38 +/- 0.21 mM and 11.9 +/- 1.5 nmol mg protein(-1) min(-1), respectively. The order of the potencies of unlabeled biguanides to inhibit [14C]metformin transport by hOCT2 was phenformin > buformin > metformin. Furthermore, [C-14]metformin transport was inhibited slightly or moderately by cationic drugs such as procainamide and quinidine at respective therapeutic concentrations. Conclusions. Metformin is transported by the basolateral organic cation transporter hOCT2 in the human kidney. hOCT2 could play a role in the drug interactions between metformin and some cationic drugs.