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, Ken Ichi Inui

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)379-386
Number of pages8
JournalDrug metabolism and pharmacokinetics
Volume20
Issue number5
DOIs
Publication statusPublished - Oct 2005

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Metformin
Cations
Kidney
Liver
Complementary DNA
HEK293 Cells
Pharmaceutical Preparations
Type 2 Diabetes Mellitus
Transfection
Plasmids
Pharmacokinetics
Urine
Pharmacology
Ions
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. / Kimura, Naoko; Masuda, Satohiro; Tanihara, Yuko; Ueo, Harumasa; Okuda, Masahiro; Katsura, Toshiya; Inui, Ken Ichi.

In: Drug metabolism and pharmacokinetics, Vol. 20, No. 5, 10.2005, p. 379-386.

Research output: Contribution to journalArticle

Kimura, N, Masuda, S, Tanihara, Y, Ueo, H, Okuda, M, Katsura, T & Inui, KI 2005, 'Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1.', Drug metabolism and pharmacokinetics, vol. 20, no. 5, pp. 379-386. https://doi.org/10.2133/dmpk.20.379
Kimura, Naoko ; Masuda, Satohiro ; Tanihara, Yuko ; Ueo, Harumasa ; Okuda, Masahiro ; Katsura, Toshiya ; Inui, Ken Ichi. / Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. In: Drug metabolism and pharmacokinetics. 2005 ; Vol. 20, No. 5. pp. 379-386.
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