Sekikawa H, Yagi N, Oda K, Kenmotsu H, Takada M, Chen H F, Lin E T, Benet L Z
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Biol Pharm Bull. 1995 Mar;18(3):447-53. doi: 10.1248/bpb.18.447.
Furosemide (F) was administered to rabbits intravenously and intraduodenaly and the biliary excretion was studied. The major metabolite excreted in bile 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.
将速尿（F）静脉内和十二指肠内给予兔子，并研究其胆汁排泄情况。胆汁中排泄的主要代谢产物是速尿葡萄糖醛酸苷（FG）。F以及FG的酰基迁移异构体（FG-iso）也排泄到胆汁中。十二指肠内给予F后，总F（F+FG+FG-iso）的胆汁排泄率远低于静脉内给药后的排泄率。十二指肠内给予F后，胆汁中（F+FG-iso）的比例高于静脉内给药后的比例。研究了FG或FG-iso在兔子十二指肠匀浆的胆汁和上清液中的稳定性。FG在两种介质中均不稳定，其降解在两种介质中均遵循明显的一级动力学。在胆汁中，FG降解产生几种FG-iso和F，而在十二指肠匀浆的上清液中，它立即水解为F。在上清液中几乎检测不到FG-iso。这些结果表明，胆汁中排泄的FG容易降解为FG-iso和F。FG可能在十二指肠中容易被酶水解为F，产生的F可能从肠道重新吸收。未吸收的FG-iso和F可能随粪便排出。
