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 herit able hyperlipidemic (WHHL) rabbits, a low density lipoprotein (LDL) re ceptor deficient animal model for 6 weeks at doses of 12.5 mg/kg, 25 m g/kg, and 50 mg/kg. Total cholesterol levels in serum, in very low den sity lipoproteins (VLDL), in intermediate density lipoprotein, and in LDL decreased dose-dependently In the 50 mg/kg group, cholesterol redu ction in each of the aforementioned segments was 50 %, 91 %, 94 % and 33 %, respectively. The secretion rate of VLDL-cholesterol, as determi ned by intravenous injection of Triton WR-1339, also decreased in a do se-dependent manner, showing a reduction of 16 % (P < 0.05) in the 50 mg/kg group. In addition, the cholesterol content of newly-secreted VL DL also decreased dose-dependently. These results indicate that fluvas tatin sodium has a potent hypolipidemic effect, and suggest that one o f the mechanisms responsible for the reduction of serum cholesterol ma y be the suppression of VLDL-cholesterol secretion.