Effect of oral chenodeoxycholic acid on bile acid kinetics and biliary lipid composition in women with cholelithiasis

Abstract

Bile acid kinetics and biliary lipid composition were characterized in 6 women with gallstones before and after 6 mth of oral therapy with chenodeoxycholic acid, an agent that induces dissolution of cholesterol gallstones in man. Over a dosage range of 1 to 4 g/day, absorption varied from 0.8 to 2.3 g/day. The chenodeoxycholic acid pool expanded 2 to 6 fold, and bile became composed predominantly (> 90%) of chenodeoxycholic acid conjugated chiefly with glycine. Cholic acid and deoxycholic acid pools decreased markedly, so that the total bile acid pool expanded much less, about 2 fold on the average. Cholic acid synthesis decreased in 5 of the 6 patients, consistent with negative feedback inhibition of cholic acid synthesis by chenodeoxycholic acid. In 4 patients whose bile was above or close to saturation with cholesterol, the bile became unsaturated; in 2 patients, whose bile was unsaturated, it remained so. In 5 patients with radiolucent gallstones, chenodeoxycholic acid therapy was continued after completion of kinetic and composition measurements; the stones decreased in size or dissolved entirely during the subsequent 6 to 18 mth. Similar measurements of bile acid kinetics and biliary lipid composition were made before and after a 6 mth period without medication in a control group of 6 healthy women; no changes occurred.