Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1.
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Kimura N, Masuda S, Tanihara Y, Ueo H, Okuda M, Katsura T, Inui K
Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1.
Drug Metab Pharmacokinet. 2005 Oct;20(5):379-86.
- PubMed ID
- 16272756 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Metformin Solute carrier family 22 member 2 Protein Humans UnknownSubstrateInhibitorDetails - Polypeptides
Name UniProt ID Solute carrier family 22 member 2 O15244 Details Solute carrier family 22 member 1 O15245 Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareDalfampridineMetformin The serum concentration of Dalfampridine can be increased when it is combined with Metformin. MetforminLamotrigine The serum concentration of Metformin can be increased when it is combined with Lamotrigine.