Influence of Cholestasis on Absorption of Ursodeoxycholic Acid

Ursodeoxycholic acid (UDCA) has beneficialeffects in cholestatic liver diseases. Absorption ofUDCA is slow and incomplete. In the present study theeffect of cholestasis on absorption was evaluated in 10 patients with pancreatic carcinoma andextrahepatic biliary drainage. At days 3 and 10 afterinsertion of the biliary drain, all patients received750 mg UDCA in three divided doses. On both occasions intestinal absorption of UDCA was determined toevaluate the influence of cholestasis. Serum bilirubinwas used as indicator of cholestasis. Biliary output ofUDCA served as measure of absorption and was determined by gas-liquid chromatography. Atdays 4 and 11 bile consisted of less than 2% of UDCA,indicating that UDCA excretion was complete within 24 hrand no accumulation of UDCA had occurred. After insertion of the drain, serum bilirubindecreased from 12.2 ± 2.4 mg/dl at day 3 to 5.4± 0.9 mg/dl at day 10. Biliary secretion of bileacids increased from 2.0 ± 0.3 to 3.1 ±0.4 mmol/day, whereas percentage of ursodeoxycholic acid in bile didnot significantly increase (41.1% vs 42.1%). Absorptionof UDCA increased from 39.8 ± 5.0% to 61.1± 6.2% of the administered dose, indicating animprovement of the absorption rate after decrease ofcholestasis by 53.65% (P < 0.05). In conclusion, insevere cholestasis absorption of orally administeredUDCA is markedly reduced. This may have implications in the treatment of patients with cholestaticdisease.