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Motohashi, H. et al.

Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A).

Histamine H2 receptor antagonist famotidine and cimetidine are commonly used for treatment of gastrointestinal ulcer diseases. Inasmuch as these drugs are mainly secreted by renal tubules, dosages have been adjusted according to renal function. Although many studies have been performed on the molecular mechanisms of renal handling of cimetidine, little is known about that of famotidine. In this study, to examine the recognition and transport of famotidine by human organic anion transporters (OATs; hOAT1, hOAT3) and human organic cation transporter ( OCT; hOCT2), the uptake studies using Xenopus laevis oocytes were performed in comparison with cimetidine. The half-maximal inhibitory concentrations of famotidine for [3H]estrone sulfate transport by hOAT3 and [14C]tetraethylammonium transport by hOCT2 (300 microM and 1.8 mM, respectively) were higher than those of cimetidine (53 and 67 microM, respectively). While cimetidine inhibited p-[14C]aminohippurate transport by hOAT1 in a concentration dependent manner, famotidine did not affect it at 5 mM. In addition, hOAT3 mediated famotidine uptake, but hOAT1 and hOCT2 did not show famotidine transport. These results indicate that there are marked differences between famotidine and cimetidine in the recognition and transport by organic ion transporters and that hOAT3 contributes to the renal tubular secretion of famotidine. Present findings should be useful information to understand the renal handling of famotidine and cimetidine.[1]

References

Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Motohashi, H., Uwai, Y., Hiramoto, K., Okuda, M., Inui, K. Eur. J. Pharmacol. (2004) [Pubmed]

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