Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase

Abstract

The fungal metabolite ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, has been shown to be significantly effective in lowering serum cholesterol levels in cynomolgus monkeys at doses of 20-50 mg/kg per day. Levels of serum phospholipids and triglycerides were, however, not significantly changed by the administration of the drug. Of the serum lipoprotein fractions, a beta-lipoprotein corresponding to low density lipoprotein was preferentially reduced by the drug treatment. Fecal excretion of neutral sterols was unaffected but that of bile acids and slightly elevated by the administration of ML-236B.