Metabolism of 3,7-dioxo-5.BETA.-cholanoic acid in the biliary fistula rodents and rabbits.

Abstract

Intestinal absorption and metabolism of 3,7-dioxo-5 beta-cholanoic acid, were studied in the bile fistula rats, hamsters, guinea-pigs and rabbits. The influence of dose (1 and 100 mg/kg) on the absorption and the metabolism was also estimated. The dioxo bile acid was absorbed efficiently from the intestine and quickly excreted into bile in these animals. Large dose did not retard the absorption rate and showed a significant choleretic effect for a few hours. Species differences were observed in the metabolism of this compound. In hamsters and guinea-pigs, most of the metabolites in the bile were conjugated with either taurine or glycine. The proportion of bile acids amidated with glycine was greater with the large dose. In rats, the biliary metabolites were conjugated with taurine, but not with glycine, whereas in rabbits, glycine conjugates were the only recovered metabolites. Unconjugated metabolites were also detected in the bile of the rodents, and the proportion of them rose to 17-29% after the administration of 100 mg/kg quantities. A small part of unchanged 3,7-dioxo-5 beta-cholanoic acid was excreted into the bile as both the conjugated and unconjugated forms in these animals. The greater part of this compound administered was metabolized to 7-ketolithocholic acid, chenodeoxycholic acid and ursodeoxycholic acid. In hamsters and guinea-pigs, chenodeoxycholic acid was a greater metabolite of this compound than ursodeoxycholic acid, while in rats and rabbits, the amount of ursodeoxycholic acid exceeded that of chenodeoxycholic acid. In rats, the resulting dihydroxy bile acids were further metabolized to alpha- and beta-muricholic acids.