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

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

Volume: 2 Issue: 7

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

Affiliation:

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

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.

Cite this article as:

Muller Ingo, Hagos Yohannes, Burckhardt Gerhard and Burckhardt C. Birgitta, Interaction of Furosemide with the Human Sodium-Dependent Dicarboxylate Transporter (hNaDC-3), Letters in Drug Design & Discovery 2005; 2 (7) . https://dx.doi.org/10.2174/157018005774479087