title: 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.
abstract: 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.
authors: Institute for Experimental Animals, Kobe University School of Medicine, Japan.
authors: M
authors: M
authors: Shiomi
authors: M
authors: M
authors: Shiraishi
authors: T
authors: T
authors: Yata
authors: T
authors: T
authors: Ito
mesh_terms: 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
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008055:Lipids; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D000077340:Fluvastatin; D002784:Cholesterol