Luoma P V, Sotaniemi E A, Pelkonen R O, Pirttiaho H I
Eur J Clin Pharmacol. 1985;28(6):615-8. doi: 10.1007/BF00607903.
Serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentration and the ratio between them, major risk factors of coronary heart disease, and liver size were investigated in 18 subjects who were on enzyme-inducing anticonvulsants, phenytoin alone or in combination with phenobarbital and/or carbamazepine. The subjects with a high liver cytochrome P-450, indicating hepatic microsomal enzyme induction, who showed an increase in liver size, had an elevated high-density lipoprotein concentration and high-density lipoprotein cholesterol/total cholesterol ratio, and a reduced low/high-density lipoprotein cholesterol ratio. The high-density lipoprotein cholesterol concentration and its ratio to total cholesterol were directly and related to the ratio between low and high-density lipoprotein cholesterol were inversely related to the extent of liver enlargement. The serum cholesterol distribution profile associated with an increase in liver size was typical of subjects with a low risk of coronary heart disease. The results suggest that enzyme-inducers, such as phenytoin and phenobarbital, induce structural and functional changes in hepatocellular membranes associated with liver enlargement and cholesterol distribution characteristic of low susceptibility to atherosclerotic vascular disease.
对18名服用酶诱导性抗惊厥药(单独使用苯妥英或与苯巴比妥和/或卡马西平联合使用)的受试者进行了研究,检测了他们的血清低密度脂蛋白胆固醇和高密度脂蛋白胆固醇浓度及其比值(冠心病的主要危险因素)以及肝脏大小。肝脏细胞色素P - 450水平高表明肝微粒体酶被诱导,这类受试者肝脏大小增加,高密度脂蛋白浓度和高密度脂蛋白胆固醇/总胆固醇比值升高,而低密度/高密度脂蛋白胆固醇比值降低。高密度脂蛋白胆固醇浓度及其与总胆固醇的比值与低密度和高密度脂蛋白胆固醇之间的比值直接相关,而与肝脏肿大程度呈负相关。与肝脏大小增加相关的血清胆固醇分布特征是冠心病低风险受试者的典型特征。结果表明,苯妥英和苯巴比妥等酶诱导剂可诱导肝细胞膜的结构和功能变化,这些变化与肝脏肿大以及对动脉粥样硬化性血管疾病低易感性的胆固醇分布特征有关。