Crilvastatin is a new
drug from the
pyrrolidone family, which acts as a non-competitive inhibitor of
3-hydroxy-3-methylglutaryl-coenzyme A reductase. The long-term effects of oral
crilvastatin treatment (200 mg 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 efficiently inhibited
cholesterol synthesis in liver and intestine, as shown by the decreased incorporation of exogenous [14C]
acetate into hepatic (3.5-fold in SW, 1.7-fold in RICO rats) and intestinal (2.5-fold in SW, 3.3-fold in RICO rats)
sterols. In RICO rats in which the
dietary cholesterol absorption coefficient was two-fold lower in treated (38%) than in untreated (78%) rats, this
drug reduced intestinal
cholesterol absorption. As a result, the total plasma
cholesterol input (absorption + synthesis), measured by
isotope analysis in RICO rats, was markedly lower in treated (11.3 mg per day) than in untreated animals (28.8 mg per day).