Effect of simvastatin (MK-733) on sterol and bile acid excretion in rabbits.
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 both diet groups. Cholestyramine altered fecal and biliary composition of bile acids, but MK-733 did not. It was considered that MK-733 inhibited the absorption of cholesterol, resulting in an increase of the fecal concentration 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.
Ishida
F
F
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Iizuka
Y
Y
Kakubari
K
K
Kurahashi
Y
Y
Sawasaki
Y
Y
Kamei
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology; D002792:Cholestyramine Resin / Q000494:pharmacology; D005243:Feces / Q000032:analysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D019821:Simvastatin; D013261:Sterols / Q000378:metabolism*
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D013261:Sterols; D002792:Cholestyramine Resin; D008148:Lovastatin; D019821:Simvastatin