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 Treatment has been withdrawn from 1.9% of patients receiving the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.