Pharmacokinetics and metabolism of [14C]ursodeoxycholic acid in the rat

The pharmacokinetics and metabolism of [14C]ursodeoxycholic acid have been studied after intravenous and intraduodenal administrations of tracer doses to bile fistula rats. Control animals were fed a standard diet. Two other groups received the same diet added with UDCA (5 mg/kg body wt. per day) (group A) or (20 mg/kg body wt. per day) (group B) for 3 weeks. The plasma clearance in control and treated animals after intravenous injection of [14C]UDCA (2 microCi. 20 microgram) followed an identical biphasic exponential curve with t 1/2 of 2 and 30 min, respectively. Biliary excretion kinetics were dependent on the treatment; after 10 min of injection, the recovery of radioactivity in bile was 29.8, 19 and 10.9% in group B, A and control, respectively. After intraduodenal administration, the same dose of [14C]UDCA, was rapidly absorbed and excreted in bile. The kinetic process was modified by treatment; at the 30-min peak of radioactivity, the fraction of the dose excreted in bile was: controls, 51.2%; group A, 32.8% and group B, 35.3%. Biotransformation of [14C]UDCA after intravenous and intraduodenal administrations was similar in the three groups. Radioactivity was mainly found as the tauroconjugate of UDCA and less than 5% 14C was recovered as beta-muricholic acid. Bile composition was modified by the UDCA diet as follows: biliary bile acids increased and cholesterol decreased proportionally to the dose; the relative ratio of biliary bile acids was changed, UDCA represented at most 7% in the group B.