Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine.

Abstract

The aim of this study was to evaluate the biotransformation of orally administered ursodeoxycholic acid in man. The distribution of ursodeoxycholic acid and its metabolites in gallbladder bile, in serum and in urine with emphasis on separation of their unconjugated, amidated and sulfated species in particular, was investigated. Seven gallstone patients were given 750 mg of ursodeoxycholic acid daily for 2-3 weeks. Six gallstone patients who did not receive ursodeoxycholic acid served as controls. Ursodeoxycholic acid became the major bile acid in gallbladder bile contributing 43% to total bile acids. 2% of biliary ursodeoxycholic acids were in the unconjugated form, 87% in the amidated form and 11% in the sulfated form. Iso-ursodeoxycholic acid was found in bile in small amounts and was present only as the sulfated species and not as the amidated one. Other metabolites of ursodeoxycholic acid tentatively identified in bile were 1 beta, 12 beta, 6 alpha- and 21,22-hydroxylated derivatives of ursodeoxycholic acid. Lithocholic acid in bile tended to increase under ursodeoxycholic acid treatment and was positively correlated to ursodeoxycholic acid. The concentration of cholic acid in bile decreased significantly whereas the levels of deoxycholic acid and chenodeoxycholic acid did not change. Total bile acid concentration in serum and excretion of bile acids in urine increased from 5.4 +/- 1.1 to 18.4 +/- 9.5 mumol l-1 (mean +/- SD, P < 0.005) and from 5.6 +/- 1.3 to 13.1 +/- 7.9 mumol g-1 creatinine (mean +/- SD, P < 0.05) after ursodeoxycholic acid ingestion mainly due to spillover and excretion of ursodeoxycholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)