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

Access this Article

Author(s)

    • KIMURA Naoko
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • MASUDA Satohiro
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • TANIHARA Yuko
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • UEO Harumasa
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • OKUDA Masahiro
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • KATSURA Toshiya
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University
    • INUI Ken-ichi
    • Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University

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 <i>in vivo</i> 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.<br>

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 20(5), 379-386, 2005

    The Japanese Society for the Study of Xenobiotics

Codes

  • NII Article ID (NAID)
    130004462974
  • Text Lang
    ENG
  • ISSN
    1347-4367
  • Data Source
    J-STAGE 
Page Top