title: Biliary excretion of furosemide glucuronide in rabbits.
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sekikawa
authors.forename: N
authors.initials: N
authors.lastname: Yagi
authors.forename: K
authors.initials: K
authors.lastname: Oda
authors.forename: H
authors.initials: H
authors.lastname: Kenmotsu
authors.forename: M
authors.initials: M
authors.lastname: Takada
authors.forename: H F
authors.initials: HF
authors.lastname: Chen
authors.forename: E T
authors.initials: ET
authors.lastname: Lin
authors.forename: L Z
authors.initials: LZ
authors.lastname: Benet
mesh_terms: D000328:Adult; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001659:Biliary Tract / Q000378:metabolism*; D004355:Drug Stability; D004386:Duodenum / Q000737:chemistry / Q000378:metabolism; D005665:Furosemide / Q000378:metabolism / Q000493:pharmacokinetics*; D005965:Glucuronates / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits
chemical_list: D005965:Glucuronates; D005665:Furosemide