Effects of MK-733, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on absorption and excretion of [3H]cholesterol in rabbits.
Effects of MK-733 on the absorption and excretion of cholesterol in rabbits were examined using [3H]cholesterol. The animals were divided into six groups; three groups were fed a normal diet, and the other groups a cholesterol diet. MK-733 was administered orally as a single dose of 10 mg/kg on day 8, or multiple doses of 10 mg/kg once a day for 14 days. On the 8th day, [3H]cholesterol was given orally to each animal. In the groups fed a normal diet, single and consecutive administration of MK-733 did not affect the absorption and excretion of [3H]cholesterol. In the cholesterol-fed groups, however, single administration of MK-733 decreased the serum 3H radioactivity slightly, but did not affect the fecal excretion of [3H]cholesterol. However, the consecutive treatment with MK-733 clearly reduced the serum 3H radioactivity. The cumulative excretion of the fecal radioactivity of [3H]cholesterol in the MK-733 group (multiple) was higher than that in the control group. From these results, it is concluded that MK-733 inhibits the absorption of cholesterol from the gastrointestinal wall in cholesterol-fed rabbits.
Ishida
F
F
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Sato
A
A
Iizuka
Y
Y
Sawasaki
Y
Y
Aizawa
A
A
Kamei
T
T
D000284:Administration, Oral; D000818:Animals; D002784:Cholesterol / Q000493:pharmacokinetics*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005243:Feces / Q000032:analysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D019821:Simvastatin; D012855:Sitosterols / Q000494:pharmacology
D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012855:Sitosterols; C025473:gamma-sitosterol; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin