Low dose ursodeoxycholic acid at bedtime and at mealtimes: Effect on mass of lipids within the gallbladder and on gallstone dissolution rate

Objective: To compare the effect of bedtime and mealtime administration of low dose ursodeoxycholic acid (UDCA) (3-5 mg/kg per day) in gallstone patients on cholesterol saturation index, total mass of biliary lipids within the gallbladder and gallstone dissolution rate. Design: Patients were randomly allocated to either bedtime or mealtime UDCA at a dose similar to that used for gallstone dissolution in combination with chenodeoxycholic acid (CDCA). Methods: In 18 patients with radiolucent gallstones in radiologically functioning gallbladders we measured the total mass of biliary lipids within the gallbladder before and after 1 month of UDCA therapy by gallbladder bile sampling and cholescintigraphy; gallstone dissolution rate was measured after 6 and 12 months of therapy. Results: The dissolution rate was faster for the bedtime regimen (n = 9) than for the mealtime regimen (n = 9), both at 6 months (medians: 40 versus 0%, P <0.05) and at 12 months (70 versus 0%, P <0.05). In the whole group (n = 12), the saturation index was significantly reduced during therapy: this was caused by significantly reduced cholesterol mass within the gallbladder, without changes in the bile acid or phospholipid masses. There was no difference between the two dose timings for saturation index or for the lipid masses within the gallbladder. Conclusions: Using a low dose of UDCA, bedtime administration is more efficacious than mealtime administration for cholesterol gallstone dissolution; the reduction in saturation index is due only to a reduction of cholesterol mass within the gallbladder. These findings suggest that combination therapy involving low doses of both UDCA and CDCA should also be given at bedtime.