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 six women with gallstones before and after 6 mo of oral therapy with chenodeoxycholic acid, an agent that induces dissolution of cholesterol gallstones in man. Over a dosage range of 1-4 g/day, absorption varied from 0.8 to 2.3 g/day. The chenodeoxycholic acid pool expanded two-to sixfold, 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 twofold on the average. Cholic acid synthesis decreased in five of the six patients, consistent with negative feedback inhibition of cholic acid synthesis by chenodeoxycholic acid. In four patients whose bile was above or close to saturation with cholesterol, the bile became unsaturated; in two patients, whose bile was unsaturated, it remained so. In five 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 mo. Similar measurements of bile acid kinetics and biliary lipid composition were made before and after a 6-mo period without medication in a control group of six healthy women; no changes occurred.