Journal of Lipid Research, Vol 34, 429-435, Copyright © 1993 by Lipid Research, Inc.

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Metabolism of sulfonate analogs of ursodeoxycholic acid and their effects on biliary bile acid composition in hamsters

T Mikami, K Kihira, S Ikawa, M Yoshii, S Miki, EH Mosbach and T Hoshita
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.

The metabolism of sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24- sulfonate and sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23- sulfonate was studied in hamsters. In bile fistula animals these sulfonate analogs of ursodeoxycholic acid were absorbed mainly from the terminal ileum and secreted rapidly into the bile without biotransformation or conjugation. After oral administration, the sulfonate analogs were excreted in the feces at the same rate as chenodeoxycholic acid and its metabolic products. The intestinal microorganisms transformed chenodeoxycholic acid largely into lithocholic acid; the sulfonate analogs were completely resistant to biotransformation. After a 2-week feeding period, the sulfonate analogs of ursodeoxycholic acid accounted for 24.0% and 16.9% of total biliary bile acids. These sulfonates did not affect the proportions of the natural bile acids in the bile, and the ratio of glycine-conjugated bile acids to taurine-conjugated bile acids was not altered by feeding the sulfonates. In contrast, when ursodeoxycholic acid was fed, the proportions of the natural bile acids and the glycine/taurine ratio were changed. These results suggest that the sulfonate analogs had no profound effect on endogenous bile acid metabolism and did not cause a depletion of the hepatic taurine pool during enterohepatic circulation. The sulfonates had no effect on intestinal cholesterol absorption and serum cholesterol levels.
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