title: Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Hospital Utrecht, Department of Gastroenterology, The Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: van de Meeberg
authors.forename: F H
authors.initials: FH
authors.lastname: Wolfhagen
authors.forename: G P
authors.initials: GP
authors.lastname: Van Berge-Henegouwen
authors.forename: J M
authors.initials: JM
authors.lastname: Salemans
authors.forename: A
authors.initials: A
authors.lastname: Tangerman
authors.forename: H R
authors.initials: HR
authors.lastname: van Buuren
authors.forename: J
authors.initials: J
authors.lastname: van Hattum
authors.forename: K J
authors.initials: KJ
authors.lastname: van Erpecum
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D015209:Cholangitis, Sclerosing / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D003840:Deoxycholic Acid / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage*; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D005723:gamma-Glutamyltransferase; D000637:Transaminases; D000469:Alkaline Phosphatase