A combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than is ursodeoxycholic acid monotherapy.

Inhibitors of 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase have been reported to decrease the cholesterol saturation index (CSI) in duodenal bile in humans and to prevent formation of cholesterol gallstones in animal studies. We performed a prospective study to evaluate the role of HMG-CoA reductase inhibitors as gallstone-dissolving agents. Fifty patients with radiolucent gallstones in a gallbladder opacifying at drip infusion cholecystography were treated with either 10 mg/day simvastatin plus 600 mg/day ursodeoxycholic acid (group 1, n=26) or 600 mg/day ursodeoxycholic acid alone (group 2, n=24) for 12 months. The ratio of solitary to multiple gallstone cases was 21:29. Plasma lipid levels were assessed and ultrasonographic examination of the gallbladder was performed at baseline and at 3-month intervals during treatment. Duodenal bile sampling was performed in five patients in each group at baseline and after 12 months of treatment. Plasma cholesterol decreased significantly in group 1 but not in group 2. In solitary gallstone cases, no significant difference in dissolution rates was observed between groups 1 (3 of 9, 33%) and 2 (4 of 12, 33%). In contrast, the dissolution rate in multiple gallstone cases was significantly higher in group 1 (12 of 17, 71%) than in group 2 (3 of 12, 25%) (p < 0.01). Bile cholesterol saturation index was significantly decreased (p < 0.01) but did not significantly differ between the two groups. These results suggest that combination therapy with simvastatin and ursodeoxycholic acid is more effective for cholesterol gallstone dissolution than ursodeoxycholic acid monotherapy in patients with multiple gallstones.

[Biliary excretion and clinical efficacy of T-3262 (tosufloxacin tosilate) administered in the treatment of cholecystitis].

T-3262 (tosufloxacin tosilate), a new oral pyridone carboxylic acid agent, was investigated for its biliary excretion and clinical efficacy and safety to evaluate its usefulness in the treatment of cholecystitis. T-3262 was administered to a total of 4 healthy volunteers for 2 days at a dose of 150 mg every 8 hours, and A-, B- or C-bile were collected using the MELTZER-LYON method at 10-11 hours after the final administration. Bile concentrations of T-3262 in 3 cases were 0.33-2.05 micrograms/ml (A-bile), 6.13-9.50 micrograms/ml (B-bile) and 1.11-2.70 micrograms/ml (C-bile). Thus, T-3262 levels in B-bile were 15-34 times higher than serum levels (0.28-0.41 micrograms/ml). Only a trace of serum concentration of T-3262 was detected in another case with the concentration in B-bile was 0.132 micrograms/ml. A total of 10 patients with cholecystitis were treated with T-3262 at a dose level of 150 mg per dose 3 times daily for 1 to 20 days. The clinical efficacy was excellent in 1 case, good in 5 cases and fair in 2 cases and unevaluable in 2 cases, thus the clinical efficacy rate was 75%. Bacteriologically, Klebsiella pneumoniae, Enterococcus faecalis and Haemophilus parahaemolyticus were isolated from biles of 3 patients before treatment. Upon the treatment, E. faecalis was eradicated and K. pneumoniae was unchanged. The fate of H. parahaemolyticus was not known because of examination was not done after treatment. Side effects were observed in 2 cases with diarrhea in 1 case and epigastric pain in another case. But those symptoms disappeared after cessation of administration of T-3262. Abnormal laboratory test values were not observed.