McKenney J M
School of Pharmacy, Medical College of Virginia-Virginia Commonwealth University, Richmond 23298.
Clin Pharm. 1988 Jan;7(1):21-36.
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 Treatment has been withdrawn from 1.9% of patients receiving the drug because of elevated aminotransferase concentrations.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.
对洛伐他汀的化学性质、药理学、药代动力学、临床疗效、剂量与用法以及不良反应进行了综述。洛伐他汀是一类名为3-羟基-3-甲基戊二酰辅酶A（HMG CoA）还原酶抑制剂的新型药理化合物中首个上市的药物。通过竞争性抑制HMG CoA还原酶，该药扰乱肝脏和外周细胞中胆固醇的生物合成。这增加了低密度脂蛋白（LDL）受体的合成，从而增加了血浆中LDL胆固醇的摄取。每日剂量为20至80毫克时，洛伐他汀可使总胆固醇和LDL胆固醇浓度降低25%至45%。它还能大幅降低甘油三酯、极低密度脂蛋白（VLDL）胆固醇和载脂蛋白B的浓度，并略微提高高密度脂蛋白（HDL）胆固醇浓度。洛伐他汀对杂合子家族性和非家族性（多基因）高胆固醇血症患者有效，但对纯合子家族性高胆固醇血症患者无效。它与胆汁酸螯合剂、烟酸和吉非贝齐联合使用也有效。建议晚上每日一次（以提高依从性）或每日两次服用洛伐他汀，以使药物的降胆固醇效果最大化。头痛和胃肠道不适是最常见的不良反应。因转氨酶浓度升高，1.9%接受该药治疗的患者已停药。洛伐他汀与晶状体混浊发生之间的关系有待进一步评估。洛伐他汀在原发性高胆固醇血症的治疗中非常有效，代表了一项重要的治疗进展。长期使用的安全性及其对冠心病的影响仍有待确定。
