CRILVASTATIN, A NEW 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITOR, INHIBITS CHOLESTEROL ABSORPTION IN GENETICALLY HYPERCHOLESTEROLEMIC RATS

Crilvastatin is a new drug from the pyrrolidone family, which acts as a non-competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. The long-term effects of oral crilvastatin treatment (200 m g per day per kg body weight for 4 and 10 weeks) were investigated on in vivo cholesterogenesis in male adult normocholesterolemic (SW) and genetically hypercholesterolemic (RICO) rats. In both strains of rats, the treatment had no effect on the plasma cholesterol level, but effi ciently inhibited cholesterol synthesis in liver and intestine, as sho wn by the decreased incorporation of exogenous [C-14]acetate into hepa tic (3.5-fold in SW, 1.7-fold in RICO rats) and intestinal (2.5-fold i n SW, 3.3-fold in RICO rats) sterols. In RICO rats in which the dietar y cholesterol absorption coefficient was two-fold lower in treated (38 %) than in untreated (78%) rats, this drug reduced intestinal choleste rol absorption. As a result, the total plasma cholesterol input (absor ption + synthesis), measured by isotope analysis in RICO rats, was mar kedly lower in treated (11.3 mg per day) than in untreated animals (28 .8 mg per day).