Lovastatin: a new cholesterol-lowering agent.

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of lovastatin are reviewed. Lovastatin is the first agent marketed in a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, the drug disrupts the biosynthesis of cholesterol in hepatic and peripheral cells. This increases the synthesis of low-density-lipoprotein (LDL) receptors and thereby increases the uptake of LDL cholesterol from the plasma. In doses of 20 to 80 mg daily, lovastatin decreases total and LDL cholesterol concentrations 25 to 45%. It also substantially reduces concentrations of triglycerides, very-low-density-lipoprotein (VLDL) cholesterol, and apolipoprotein B and slightly increases high-density-lipoprotein (HDL) cholesterol concentrations. Lovastatin is effective in patients with heterozygous familial and nonfamilial (polygenic) hypercholesterolemia but is ineffective in patients with homozygous familial hypercholesterolemia. It is also effective in combination with bile acid sequestrants, nicotinic acid, and gemfibrozil. Administration of lovastatin once daily in the evening (to enhance compliance) or twice daily is recommended to maximize the drug's cholesterol-lowering effects. Headache and gastrointestinal complaints are the most common adverse effects. Treatment has been withdrawn from 1.9% of patients receiving the drug because of elevated aminotransferase concentrations. The relationship of lovastatin to the development of lens opacities requires further evaluation. Lovastatin is highly effective in the treatment of primary hypercholesterolemia and represents an important therapeutic advance. Safety with long-term use and effect on coronary heart disease remain to be established.