Johnson B F, LaBelle P, Wilson J, Allan J, Zupkis R V, Ronca P D
Division of Clinical Pharmacology, University of Massachusetts Medical Center, Worcester, MA 01655.
Clin Pharmacol Ther. 1990 Oct;48(4):467-72. doi: 10.1038/clpt.1990.176.
Patients with non-insulin dependent diabetes mellitus (NIDDM) have a higher risk of atherosclerotic cardiovascular disease than nondiabetic subjects. In seven patients with both hypercholesterolemia and NIDDM controlled by chlorpropamide, lovastatin (20 mg b.i.d. for 6 weeks) lowered low-density lipoprotein cholesterol by 28%, total cholesterol by 24%, and apolipoprotein B by 24%. Lovastatin levels for a 4-hour period (measured as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitory activity) were similar to those measured previously in nondiabetic patients. Lovastatin did not alter chlorpropamide kinetics or glycemic profiles. No patient had an elevation in serum transaminases or creatinine phosphokinase, and no patient had any other laboratory or clinical drug-related adverse experience during the study. Lovastatin was as effective in reducing low-density lipoprotein cholesterol in patients with NIDDM as in nondiabetic subjects. Diabetic control was unaltered, and no evidence of alteration in lovastatin or chlorpropamide blood levels was noted.
非胰岛素依赖型糖尿病(NIDDM)患者患动脉粥样硬化性心血管疾病的风险高于非糖尿病患者。在7名同时患有高胆固醇血症和由氯磺丙脲控制的NIDDM患者中,洛伐他汀(每日2次,每次20mg,共6周)使低密度脂蛋白胆固醇降低了28%,总胆固醇降低了24%,载脂蛋白B降低了24%。洛伐他汀4小时的水平(以3-羟基-3-甲基戊二酰辅酶A还原酶抑制活性衡量)与之前在非糖尿病患者中测得的水平相似。洛伐他汀未改变氯磺丙脲的药代动力学或血糖情况。在研究期间,没有患者血清转氨酶或肌酸磷酸激酶升高,也没有患者出现任何其他与药物相关的实验室或临床不良事件。洛伐他汀在降低NIDDM患者低密度脂蛋白胆固醇方面与非糖尿病患者同样有效。糖尿病控制情况未改变,且未发现洛伐他汀或氯磺丙脲血药浓度有改变的迹象。