[3-3H]
Cholic acid glucuronide [7 alpha,12 alpha-dihydroxy-3 alpha-O-(beta-D-glucopyranosyluronate)-5 beta- cholan-24-oate] was synthesized and administered to rats prepared with either an external
biliary fistula or a ligated bile duct. When bile
fistula animals were given either microgram or milligram amounts of the
glucuronide, biliary secretion of label was rapid and efficient: greater than 90% of the administered label was secreted within 60 min and total recovery of label in bile was 98.6 +/- 1.2%. Studies in which [14C]
taurocholate was included in the dose indicated that this
bile acid was secreted into bile significantly more rapidly than was the
glucuronide. In animals with ligated bile ducts, urinary excretion was the major route of elimination: after 20 hr, 83.4 +/- 9.3% of the administered dose had been excreted in urine. Urinary excretion of
cholate glucuronide was significantly more rapid than that of
taurocholate. Gas-liquid chromatographic analysis of the methyl
ester acetate derivatives of labeled compounds isolated from bile and urine by chromatography established that the bulk (greater than 70%) of the administered material was secreted in bile or excreted in urine as the intact
cholate glucuronide. From these results, we conclude that the glucuronidation of
cholic acid produces a derivative which is rapidly and effectively cleared from the circulation and excreted.