Influence of cholestasis on absorption of ursodeoxycholic acid.
Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic liver diseases. Absorption of UDCA is slow and incomplete. In the present study the effect of cholestasis on absorption was evaluated in 10 patients with pancreatic carcinoma and extrahepatic biliary drainage. At days 3 and 10 after insertion of the biliary drain, all patients received 750 mg UDCA in three divided doses. On both occasions intestinal absorption of UDCA was determined to evaluate the influence of cholestasis. Serum bilirubin was used as indicator of cholestasis. Biliary output of UDCA served as measure of absorption and was determined by gas-liquid chromatography. At days 4 and 11 bile consisted of less than 2% of UDCA, indicating that UDCA excretion was complete within 24 hr and no accumulation of UDCA had occurred. After insertion of the drain, serum bilirubin decreased from 12.2 +/- 2.4 mg/dl at day 3 to 5.4 +/- 0.9 mg/dl at day 10. Biliary secretion of bile acids increased from 2.0 +/- 0.3 to 3.1 +/- 0.4 mmol/day, whereas percentage of ursodeoxycholic acid in bile did not significantly increase (41.1% vs 42.1%). Absorption of UDCA increased from 39.8 +/- 5.0% to 61.1 +/- 6.2% of the administered dose, indicating an improvement of the absorption rate after decrease of cholestasis by 53.65% (P < 0.05). In conclusion, in severe cholestasis absorption of orally administered UDCA is markedly reduced. This may have implications in the treatment of patients with cholestatic disease.
Sauer
P
P
Department of Medicine, University of Heidelberg, Germany.
Benz
C
C
Rudolph
G
G
Klöters-Plachky
P
P
Stremmel
W
W
Stiehl
A
A
D000284:Administration, Oral; D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D004322:Drainage; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D001663:Bilirubin