Effect of tauroursodeoxycholic acid on biliary lipid composition. A dose-response study.
Tauroursodeoxycholic acid has been proposed for the treatment of hepatobiliary disease, but data on the enrichment of biliary tauroursodeoxycholic acid pool and on changes of biliary lipids after administration of the compound are scarce. We studied the composition of biliary lipids in a series of 33 patients with radiolucent stones, before and after treatment with tauroursodeoxycholic acid, 3.5 - 16.6 mg/kg/day for 4 - 6 weeks. Duodenal bile was collected with the Entero-Test after gallbladder contraction. Tauroursodeoxycholic acid administration produced the following dose-dependent effects: a linear decrease of cholesterol saturation (r = 0.59, p < 0.001); a non-linear increase of the percent of ursodeoxycholic acid in bile (r = 0.59, p < 0.001); a non-linear increase of the fraction of ursodeoxycholate conjugated with taurine. At the dose of 11 mg/kg per day, cholesterol saturation was 80%, ursodeoxycholic acid represented about 45% of biliary bile acids, and about half of UDCA was conjugated with taurine. Biliary bile acids were repeatedly measured in 6 patients during long-term treatment with 9.7 - 12.1 mg/kg. The fraction of tauroursodeoxycholic acid decreased progressively from 67.6% +/- 10.5 to 29.1% +/- 5. Tauroursodeoxycholic acid is as effective as ursodeoxycholic acid on a molar basis in reducing biliary cholesterol saturation and in enriching bile with ursodeoxycholate. Moreover, tauroursodeoxycholic acid administration is associated with higher concentrations of tauroconjugates in the bile than those previously reported by feeding the free bile acid.
Muraca
M
M
Department of Internal Medicine, University of Padua, Italy.
Vilei
M T
MT
Cianci
V
V
Liu
X T
XT
Garotta
F
F
D000328:Adult; D000368:Aged; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D002769:Cholelithiasis / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D002784:Cholesterol