EFFECT OF URSODEOXYCHOLIC ACID ON THE KINETICS OF CHOLIC-ACID AND CHENODEOXYCHOLIC ACID IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS

Treatment of patients with cholestatic liver diseases with ursodeoxych olic acid has been shown to have beneficial effects that may be relate d to a shift in the balance between hydrophilic and hydrophobic bile a cids in favor of hydrophilic bile acids. During treatment of patients with primary sclerosing cholangitis with ursodeoxycholic acid, plasma concentrations of some endogenous bile acids decrease. To test whether the changes in plasma bile acids are due to decreases of their pool s izes or synthesis rates, we determined bile acid kinetics of cholic an d chenodeoxycholic acid in six patients with primary sclerosing cholan gitis, of whom four also had ulcerative colitis. All patients were stu died before and 3 mo after the start of ursodeoxycholic acid treatment . Six healthy subjects served as controls. In patients with primary sc lerosing cholangitis, pool sizes of cholic and chenodeoxycholic acid w ere considerably smaller than those in healthy controls; after ursodeo xycholic acid treatment they were unchanged. Fractional turnover and s ynthesis of cholic acid increased significantly after ursodeoxycholic acid administration. Fractional turnover of chenodeoxycholic acid also increased significantly, whereas synthesis of this bile acid was unch anged. Our data indicate that in patients with primary sclerosing chol angitis, pool sizes of bile acids are reduced. The decrease of levels of endogenous bile acids in plasma under ursodeoxycholic acid treatmen t despite unchanged bile acid pool sizes indicates redistribution of t he bile acids into the enterohepatic circulation, probably because of improved hepatic clearance after ursodeoxycholic acid treatment.