Biliary Excretion of Furosemide Glucuronide in Rabbits

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Furosemide (F) was administered to rabbits intravenously and intraduodenaly and the biliary excretion was studied. The major metabolite excreted in blle was furosemide glucuronide (FG). F and acyl migration isomers of FG (FG-iso) were also excreted in bile. The biliary excretion rates of total F (F+FG+FG-iso) following intraduodenal administration of F were much smaller than those following intravenous administration. The fraction of (F+FG-iso) in bile following intraduodenal administration of F were larger than those following intravenous administration. Stability of FG or FG-iso in bile and supernatant solution of the duodenum homogenate of rabbits was studied. FG was unstable in both media and its degradation followed apparent first-order kinetics in both media. In bile, FG degraded to produce several FG-iso and F, while in the supernatant solution of the duodenum homogenate, it hydrolyzed immediately to F. FG-iso were hardly detected in the supernatant solution. These results indicated that FG excreted in bile degraded easily to FG-iso and F. FG might easily hydrolyze to F enzymatically in the duodenum, and the resultant F might be reabsorbed from the intestinal tract. Unabsorbed FG-iso and F might be excreted in the feces.
社団法人日本薬学会の論文
1995-03-15