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 [14C]metformin was assessed by the tracer experiments in the human embryonic kidney (HEK293) cells expressing hOCT2.
Results: The transport of [14C]metformin was markedly stimulated in hOCT2-expressing cells compared with the vector-transfected cells. The accumulation of [14C]metformin was concentrative and was dependent on the membrane potential, showing consistency with the characteristics of hOCT2. The apparent Km and Vmax values of [14C]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, [14C]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.