Effect of Simvastatin (MK-733) on Sterol and Bile Acid Excretion in Rabbits

Abstract

The effects of Simvastatin (MK-733), an inhibitor of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, on fecal and biliary excretion of sterols and bile acids were examined using rabbits. Multiple doses of MK-733 (10 mg/kg/day) for 7 days were found to increase fecal concentrations of neutral sterols in cholesterol-fed rabbits, but not to affect those of bile acids. Multiple doses of cholestyramine (750 mg/kg/day), a bile acid sequestrant, for 7 days increased fecal concentrations of neutral sterols and bile acids in normally fed and cholesterol-fed groups. MK-733 did not affect biliary neutral sterols and total bile acids in normally fed and cholesterol-fed groups. Cholestyramine decreased biliary concentrations of neutral sterols in cholesterol-fed rabbits. The mechanism of action of MK-733 in the inhibition of cholesterol absorption is considered to be clearly different from that of cholestyramine. These results confirmed the conclusion in the previous experiment.