EFFECT OF TAUROURSODEOXYCHOLIC ACID ON BILIARY LIPID-COMPOSITION - A DOSE-RESPONSE STUDY

Tauroursodeoxycholic acid has been proposed for the treatment of hepat obiliary disease, but data on the enrichment of biliary tauroursodeoxy cholic acid pool and on changes of biliary lipids after administration of the compound are scarce. We studied the composition of biliary lip ids in a series of 33 patients with radiolucent stones, before and aft er treatment with tauroursodeoxycholic acid, 3.5 - 16.6 mg/kg/day for 4 - 6 weeks. Duodenal bile was collected with the Entero-Test after ga llbladder contraction. Tauroursodeoxycholic acid administration produc ed the following dose-dependent effects: a linear decrease of choleste rol saturation (r = 0.59, p < 0.001); a non-linear increase of the per cent of ursodeoxycholic acid in bile (r = 0.59, p < 0.001); a non-line ar increase of the fraction of ursodeoxycholate conjugated with taurin e. At the dose of 11 mg/kg per day, cholesterol saturation was 80%, ur sodeoxycholic acid represented about 45% of biliary bile acids, and ab out 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 prog ressively from 67.6% +/- 10.5 to 29.1% +/- 5. Tauroursodeoxycholic aci d is as effective as ursodeoxycholic acid on a molar basis in reducing biliary cholesterol saturation and in enriching bile with ursodeoxych olate. Moreover, tauroursodeoxycholic acid administration is associate d with higher concentrations of tauroconjugates in the bile than those previously reported by feeding the free bile acid.