Ursodeoxycholic Acid Treatment for
A Multicenter Double-Blind Trial
TOKYO COOPERATIVE GALLSTONE STUDY GROUP
The cholelitholytic action of ursodeoxycholic acid (LJDCA) was investigated by a double-blind clinical trial. The trial started with 153 subjects all confirmed by radiographic examination as having radiolucent gallstones in a functioning gallbladder. The subjects were divided into three groups receiving 600 mg/day of UDCA, 150 mg/day of UDCA, and placebo (lactose) per day, respectively. Seventy-nine cases were classed as dropouts or were excluded due to incomplete follow-up or inadequate patient selection, and the data on the remaining 72 cases were analyzed. After 6-22 mo of treatment, dissolution or decrease in size or number of stones occurred in 10 of the 29 cases in the 600 mg/day group (34.5%], 4 of 23 cases in the 150 mg/day group (17.4X), and 2 of 20 cases in the control group (5.0%). For those cases with noncalcified, less than 15 mm in diameter, and floating stones, efficacy increased to 83.3% in the 600 mg/day group. Lithogenic index of bile defined by Thomas and Hofmann became unsaturated after treatment in the 600 mg/day group. Neither diarrhea nor hepatic toxicity was noted. The results indicate that UDCA is a safe and effective Jitholytic agent. Ursodeoxycholic acid (UDCA) is the principal bile acid of bear bile. Bear bile has been used in Japan for many years as a folk medicine to treat dyspepsia or biliary colic. In 1972, Danzinger et al.’ reported that oral administration of chenodeoxycholic acid (CDCA) was effective in dissolving cholesterol gallstones. Ursodeoxycholic acid is the 7/3-hydroxy epimer of CDCA, and large amounts have been detected in the bile of some subjects treated with CDCA.” This indicates that it is also a litholytic agent. Sugata et al.” also suggested it in their retrospective study on cases with gallstone disappearance. Makino et al.“ were the first in 1975 to demonstrate in open clinical trial that UDCA is an effective gallstone dissolving agent. In order to gain additional information on the efficacy and safety of high and low doses of UDCA for the dissolution of gallstones, we undertook a doubleblind clinical trial using inactive placebo and daily doses of 150 mg/day and 600 mg/day of UDCA.