Simvastatin

Simvastatin is a prodrug. After absorption, it undergoes a rapid enzymic hydrolysis of a lactone ring to form the principal metabolite simvastatin β-hydroxy acid. The β-hydroxy acid acts as a potent, reversible, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that catalyzes the conversion of hydroxymethyl glutarate to mevalonate. This conversion is an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin is used in the treatment of primary hypercholesterolemia. Simvastatin is a semisynthetic derivative of lovastatin. Simvastatin is insoluble in water but is soluble in polar organic solvents. Solubility data obtained at room temperature are illustrated in this chapter.