Biliary excretion of furosemide glucuronide in rabbits.
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.
Sekikawa
H
H
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Yagi
N
N
Oda
K
K
Kenmotsu
H
H
Takada
M
M
Chen
H F
HF
Lin
E T
ET
Benet
L Z
LZ
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
D005965:Glucuronates; D005665:Furosemide