Ursodeoxycholic acid treatment of gallstones. Dose-response study and possible mechanism of action

To determine the optimum dose for the medical treatment of gallstones with ursodeoxycholic acid (U.D.C.A.), 11 non-obese patients with radiolucent gallstones were given 5 mg, 10 mg, and 15 mg U.D.C.A. kg body-weight-1 day-1 for 6 weeks each. Apart from 3 patients who required surgery for gallstone complications, treatment was well tolerated, and both dyspeptic symptoms and frequency of biliary colic were reduced. Neither diarrhoea nor hypertransaminasaemia occurred during therapy. Of 3 patients completing 6 months' treatment with an average of 8 mg U.D.C.A. kg-1 day-1, 1 showed complete and 2 partial dissolution of gallstones. There were significant correlations between the biliary cholesterol-saturation index and (i) daily dose of U.D.C.A. in mg kg-1, (ii) percentage U.D.C.A., and (iii) percentage U.D.C.A. + chenodeoxycholic acid (C.D.C.A.) in biliary bile acids. Mean gamma-glutamyl transpeptidase fell significantly during treatment, whereas other liver-function tests and hepatic histology remained normal. Mean serum-cholesterol levels did not change, and although there was a 13-35% fall in fasting serum-triglycerides, this difference was not statistically significant. U.D.C.A., like C.D.C.A., seems to act by inhibiting hepatic cholesterogenesis. In 5 patients treated with 5 mg U.D.C.A. kg-1 day-1 for 1-6 months, mean hepatic hydroxymethylglutaryl-coenzyme-A-reductase activity was 28% lower than in untreated gallstone patients. These preliminary results suggest that U.D.C.A. is as effective as C.D.C.A. in 1/2--2/3 the dose and that 10 mg U.D.C.A. kg-1 day-1 should be effective in most gallstone patients.