Comparative effects of simvastatin (MK-733) and pravastatin (CS-514) on hypercholesterolemia induced by cholesterol feeding in rabbits.
The preventive effects of simvastatin (MK-733) and pravastatin (CS-514), 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors, on hypercholesterolemia induced by 0.25% cholesterol feeding were compared in rabbits. MK-733 (6, 2 and 0.7 mg/kg) was found to prevent the increase in serum total cholesterol levels dose-dependently. High dose CS-514 (18 mg/kg) also limited the increase in the cholesterol levels, but medium (6 mg/kg) and low doses (2 mg/kg) of CS-514 were ineffective in preventing it. MK-733 inhibited the increase in VLDL and LDL cholesterol levels dose-dependently. MK-733 suppressed the increase in serum phospholipid levels. MK-733 inhibited the accumulation of cholesterol in the liver. The high dose of CS-514 also limited it. High dose MK-733 (6 mg/kg) reduced the cholesterol concentration in gallbladder bile. Neither MK-733 nor CS-514 affected bile acid excretion in the gallbladder bile. High dose MK-733 decreased the lithogenic index. MK-733 increased the number of LDL receptors, and high dose CS-514 also increased it. The suppressive effect of CS-514 on serum cholesterol levels at 18 mg/kg was found to be less than that of MK-733 at 0.7 mg/kg.
Ishida
F
F
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Watanabe
K
K
Sato
A
A
Taguchi
K
K
Kakubari
K
K
Kitani
K
K
Kamei
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D017035:Pravastatin; D011817:Rabbits; D011973:Receptors, LDL / Q000032:analysis / Q000187:drug effects; D019821:Simvastatin; D013223:Statistics as Topic; D002785:Sterol O-Acyltransferase / Q000032:analysis / Q000037:antagonists & inhibitors
D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D009281:Naphthalenes; D011973:Receptors, LDL; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D002785:Sterol O-Acyltransferase; D017035:Pravastatin