INHIBITION OF CHOLESTEROL-SYNTHESIS EX-VIVO AND IN-VIVO BY FLUVASTATIN, A NEW INHIBITOR OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE

The inhibitory effect of fluvastatin sodium (fluvastatin), a new type of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A inhibitor, on de novo c holesterol synthesis was investigated and compared with that of pravas tatin. Fluvastatin at a concentration of 12.5 mg/kg inhibited sterol s ynthesis ex vivo from [C-14]acetate in rat liver and ileum by 97-99% w ith respect to the control, while the inhibition in kidney was 55%. Th e inhibition by fluvastatin in the liver and ileum persisted for appro ximately 9 h after administration. Significant differences between flu vastatin also had an inhibitory effect on cholesterol synthesis in viv o in various tissues of rats given [C-14]acetate intraperitoneally. St erol synthesis in the liver, ileum and kidney was inhibited by over 95 % 3 h after administration of 6.25 mg/kg of fluvastatin. Significant d ifferences between fluvastatin and pravastatin were found in the liver and ileum. Fluvastatin was more potent than pravastatin in inhibiting both ex vivo and in vivo sterol synthesis in the ileum (but not in ki dney) and liver.