Effect of fluvastatin sodium on secretion of very low density lipoprotein and serum cholesterol levels. In vivo study using low density lipoprotein receptor deficient watanabe heritable hyperlipidemic rabbits.
The hypolipidemic effects of fluvastatin sodium (XU 62-320, CAS 93957-55-2), a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, were examined. Fluvastatin sodium was administered to Watanabe heritable hyperlipidemic (WHHL) rabbits, a low density lipoprotein (LDL) receptor deficient animal model, for 6 weeks at doses of 12.5 mg/kg, 25 mg/kg, and 50 mg/kg. Total cholesterol levels in serum, in very low density lipoproteins (VLDL), in intermediate density lipoprotein, and in LDL decreased dose-dependently. In the 50 mg/kg group, cholesterol reduction in each of the aforementioned segments was 50%, 91%, 94% and 33%, respectively. The secretion rate of VLDL-cholesterol, as determined by intravenous injection of Triton WR-1339, also decreased in a dose-dependent manner, showing a reduction of 16% (p < 0.05) in the 50 mg/kg group. In addition, the cholesterol content of newly-secreted VLDL also decreased dose-dependently. These results indicate that fluvastatin sodium has a potent hypolipidemic effect, and suggest that one of the mechanisms responsible for the reduction of serum cholesterol may be the suppression of VLDL-cholesterol secretion.
Shiomi
M
M
Institute for Experimental Animals, Kobe University School of Medicine, Japan.
Shiraishi
M
M
Yata
T
T
Ito
T
T
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D007211:Indoles / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood*; D011817:Rabbits; D011973:Receptors, LDL / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008055:Lipids; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D000077340:Fluvastatin; D002784:Cholesterol