Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response.
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.
van de Meeberg
P C
PC
University Hospital Utrecht, Department of Gastroenterology, The Netherlands.
Wolfhagen
F H
FH
Van Berge-Henegouwen
G P
GP
Salemans
J M
JM
Tangerman
A
A
van Buuren
H R
HR
van Hattum
J
J
van Erpecum
K J
KJ
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
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