DMPK : Vol. 20 (2005) , No. 5 pp.379-386

Metformin is a Superior Substrate for Renal Organic Cation Transporter OCT2 rather than Hepatic OCT1

Naoko KIMURA¹⁾, Satohiro MASUDA¹⁾, Yuko TANIHARA¹⁾, Harumasa UEO¹⁾, Masahiro OKUDA¹⁾, Toshiya KATSURA¹⁾ and Ken-ichi INUI¹⁾

1) Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

(Received: July 25, 2005)
(Accepted for publication: August 29, 2005)

Abstract:

Although metformin, a cationic agent for type II diabetes, shows its pharmacological effect in the liver, the drug is mainly eliminated into urine. The tissue selectivity based on the function of drug transporters is unclear. In the present study, the transport of metformin was examined using HEK293 cells transiently transfected with five human renal organic ion transporter cDNAs. Human OCT1 and OCT2, but not OAT1, OAT3 or OCT2-A, stimulated the uptake. A kinetic analysis of metformin transport demonstrated that the amount of plasmid cDNA for transfection was also important parameter to the quantitative elucidation of functional characteristics of transporters, and both human and rat OCT2 had about a 10- and 100-fold greater capacity to transport metformin than did OCT1, respectively. In male rats, the mRNA expression level of rOCT2 in the whole kidneys was 8-fold greater than that of rOCT1 in the whole liver. The in vivo distribution of metformin in rats revealed that the expression level of renal OCT2 was a key factor in the control of the concentrative accumulation of metformin in the kidney. These findings suggest that metformin is a superior substrate for renal OCT2 rather than hepatic OCT1, and renal OCT2 plays a dominant role for metformin pharmacokinetics.

Keywords:

organic cation transporter, kidney, liver, diabetes, biguanide, TEA

	To cite this article:
	“Metformin is a Superior Substrate for Renal Organic Cation Transporter OCT2 rather than Hepatic OCT1”, Naoko KIMURA, Satohiro MASUDA, Yuko TANIHARA, Harumasa UEO, Masahiro OKUDA, Toshiya KATSURA and Ken-ichi INUI, Drug Metabolism and Pharmacokinetics, Vol. 20, No. 5, pp.379-386, (2005) .

	doi:10.2133/dmpk.20.379
	JOI JST.JSTAGE/dmpk/20.379