title: Metabolism and choleretic activity of homochenodeoxycholic acid in the hamster.
abstract: The hepatic metabolism and the choleretic effect of homochenodeoxycholic acid, the C25 homologue of chenodeoxycholic acid, were investigated in the hamster. After intravenous administration of 3H-labeled homochenodeoxycholic acid into biliary fistula hamsters, more than 80% of the radioactivity was recovered in bile in 4 h. A relatively small proportion of homochenodeoxycholic acid was present in bile as the taurine (22%) or glycine (4%) conjugate. However, more than 70% of the administered compound was biotransformed into C23 bile acids. The major C23 metabolites in bile were norchenodeoxycholic acid (17%), tauronorchenodeoxycholic acid (33%), and a trihydroxy norbile acid (identified as 3 alpha, 5 beta, 7 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic acid, 19%). Small amounts (< 5%) of sulfate(s) and glucuronide(s) were also detected. Homochenodeoxycholic acid, when infused intravenously into the hamster, produced a striking choleresis. The increase in bile flow after infusion of this compound was 6- to 7-times that induced by chenodeoxycholic acid. The apparent choleretic activity of homochenodeoxycholic acid, 181 microliters/mumol, was much greater than that of chenodeoxycholic acid, 11 microliters/mumol. In conclusion, homochenodeoxycholic acid induced a hypercholeresis of the same order of magnitude as norchenodeoxycholic acid, presumably because considerable proportions of this compound were degraded to the hypercholeretic norchenodeoxycholic acid via beta-oxidation in the liver.
authors.affiliation: Department of Surgery, Beth Israel Medical Center, New York, NY 10003.
authors.forename: S
authors.initials: S
authors.lastname: Miki
authors.forename: B I
authors.initials: BI
authors.lastname: Cohen
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: E H
authors.initials: EH
authors.lastname: Mosbach
mesh_terms: D000818:Animals; D001658:Biliary Fistula; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002756:Cholagogues and Choleretics / Q000378:metabolism / Q000494:pharmacology*; D006224:Cricetinae; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus
chemical_list: D002756:Cholagogues and Choleretics; D002635:Chenodeoxycholic Acid; C082745:homochenodeoxycholic acid