Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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Interaction of Furosemide with the Human Sodium-Dependent Dicarboxylate Transporter (hNaDC-3)

Author(s): Ingo Muller, Yohannes Hagos, Gerhard Burckhardt, Birgitta C. Burckhardt.

Abstract:

Renal elimination of drugs bound to plasma proteins is mediated mainly by tubular secretion. Furosemide, a frequently used diuretic, is tightly bound to plasma proteins and is believed to be secreted. It contains a carboxyl group and a sulfamoyl moiety and may therefore be a substrate for the sodium-dependent dicarboxylate cotransporter from human kidney (hNaDC-3). Furosemide, besides inhibiting [14C]succinate uptake, reduced succinate-associated currents in a dose-dependent manner with an IC50 of 2.2 mM. Furosemide showed sodium-dependent inward currents as evidence for its translocation by hNaDC-3. The concentrations necessary to affect hNaDC-3, however, are far higher than the therapeutically relevant plasma concentrations of furosemide. This implies that dicarboxylate uptake necessary for drug excretion via organic anion/dicarboxylate exchange will not be altered by therapeutical doses of furosemide.

Keywords: Furosemide, human kidney, organic anion transporters 1 and 3, sodium-dependent dicarboxylate transporter

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Article Details

VOLUME: 2
ISSUE: 7
Year: 2005
Page: [567 - 570]
Pages: 4
DOI: 10.2174/157018005774479087
Price: $58