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 (P SC), Since UDCA acts partly by reducing the intestinal absorption of h ydrophobic endogenous bile salts and is poorly absorbed from the intes tine, a multiple dose regimen has been advocated, Single dose treatmen t, on the other hand, may improve compliance, Aim: The effects of a si ngle or multiple dose regimen on liver enzymes and serum and biliary b ile 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 treatmen t regimens in random order with a 1-month wash-out period in between, Results: Liver biochemistry equally improved in both groups, Biliary e nrichment (%UDCA of total bile salts, mean+/-SEM) was 40.1+/-2.4 in th e single dose group vs 40.8+/-2.8 in the multiple dose group (p=NS) an d 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=8 .01). Biochemical improvement was not correlated with the concentratio n or %UDCA in serum, Patients participating in the cross-over design h ad comparable biochemical response and biliary %UDCA during both regim ens, Conclusion: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver diseas e. Biochemical improvement appears to be related to biliary (but not s erum) enrichment with UDCA.