Feasibility of low-dose and intermittent chenodeoxycholic acid therapy of gallstones

Chenodeoxycholic acid, by reducing the concentration of biliary cholesterol relative to that of bile acid and phospholipid, dissolves cholesterol gallstones. This bile acid, however, has potential dose-related hepatotoxicity and causes dose-related diarrhea. Therefore, the feasibility of low-dose and intermittent therapy was assessed by studying the induction and persistence of chenodeoxycholic acid-induced biliary lipid changes. Biliary lipid composition with each of 3 doses of chenodeoxycholic acid was determined in bile samples obtained by cholecystokinin-stimulated duodenal drainage before, after one week and one month of treatment, and up to 9 weeks after discontinuation of treatment. The lowest dose that significantly reduced the relative concentration of biliary cholesterol was 250 mg/day. A significant reduction occurred one week after initiation of treatment and was maintained for 9 weeks following discontinuation of treatment. Thus, clinical trials on low-dose and intermittent chenodeoxycholic acid therapy for gallstone prophylaxis or dissolution are warranted.