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Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response
Authors:Paul C. van de Meeberg   Frank H. J. Wolfhagen   Gerard P. Van Berge-Henegouwen   Jan M. J. I. Salemans   Albert Tangerman   Henk R. van Buuren   Jan van Hattum  Karel J. van Erpecum
Affiliation:aUniversity Hospital Utrecht, Department of Gastroenterology, Utrecht, The Netherlands;bUniversity Hospital “Dijkzigt” Rotterdam, Department of Internal Medicine II, Rotterdam, The Netherlands;cUniersity Hospital Nijmegen, Department of Gastroenterology, Nijmegen, The Netherlands
Abstract:
Background: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance.Aim: The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated.Methods: Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg−1 day−1) in a single dose at bed time (n=13) or in three divided gifts with meals (n=14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between.Results: Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean±SEM) was 40.1±2.4 in the single dose group vs 40.8±2.8 in the multiple dose group (p=NS) and was positively correlated with biochemical improvement (AP: r=0.47, p=0.02; GGT: r=0.58, p=0.002; ASAT: r=0.67, p=0.002; ALAT: r=0.52, p=0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens.Conclusion: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.
Keywords:Cholestasis   Drug therapy   Primary biliary cirrhosis   Primary sclerosing cholangitis   Ursodeoxycholic acid.
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