Metabolism of bile acids. I. Absorption, distribution, excretion, and metabolism of ursodeoxycholic acid

Abstract

The fate after oral or intravenous administration of ursodeoxycholic acid [24-14C], the major constituent of the Chinese drug Yutan (dried bear's gall), was investigated in mice and bile-fistula rats. The orally administered bile acid was mostly distributed in the liver, bile, and gastrointestinal tract after instantaneous absorption, while the radioactivity was scarcely found in other tissues and organs. Similar result was obtained after intravenous administration of the acid. In both cases, most of the radioactivity excreted was in feces, with negligible amounts in repitorary CO2 and the urine. In the liver, on the other hand, ursodeoxycholic acid was found to be converted into tauroursodeoxycholate, a part of which was hydroxylated at 6β-position to form tanro-β-muricholate. In the intestinal tract, these conjugated bile acids were hydrolyzed into the corresponding free bile acids and considerable part of free ursodeoxycholic acid was further metabolized to lithocholic acid with loss of 7β-hydroxyl group, propably by the action of microorganisms. Main radioactive metabolites excreted in feces were thus identified as ursodeoxycholic, β-muricholic, and lithocholic acids.