Effects of Antiepileptic Drugs on Lipids, Homocysteine, and C-Reactive Protein
Effects of Antiepileptic Drugs on Lipids, Homocysteine, and C-Reactive Protein
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DOI：
10.1002/ana.21615
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发表时间：
2009-04-01
影响因子：
11.2
通讯作者：
Sperling, Michael R.
中科院分区：
文献类型：
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作者：
Mintzer, Scott;Skidmore, Christopher T.;Sperling, Michael R.
目的：广泛使用的抗惊厥药苯妥英和卡马西平是细胞色素P450酶的强效诱导剂，该酶参与胆固醇合成。我们试图确定这些药物是否对胆固醇和其他血清学标志物的血管risk.Methods的影响：我们招募了34例癫痫患者服用卡马西平或苯妥英钠单药治疗的医生选择改变治疗的非诱导抗惊厥药拉莫三嗪或左乙拉西坦。在转换前和转换后6周采集空腹血液样本，以测量血清脂质成分、脂蛋白（a）、C反应蛋白和高半胱氨酸。结果：癫痫患者从苯妥英钠或卡马西平转换为苯妥英钠或卡马西平后，总胆固醇显著下降（-24.8 mg/dl），致动脉粥样硬化（非高密度脂蛋白）胆固醇（-19.9mg/dl）、甘油三酯（-47.1mg/dl）（所有p < 0.0001）和C-反应蛋白（-31.4%; p = 0.027）。停止服用卡马西平的患者脂蛋白（a）水平也下降了31.2%（p = 0.0004），而停止服用苯妥英的患者同型半胱氨酸水平下降了（-1.7 μ mol/L; p = 0.005）。所有这些变化与健康受试者相比均具有显著性（p < 0.05）。结果是相似的患者是否切换到拉莫三嗪或levetiracetam.Interpretation：切换癫痫患者的酶诱导剂卡马西平或苯妥英钠的非诱导药物levetiracetam或拉莫三嗪产生快速和临床显着改善血管风险的几个血清学标志物。这些结果表明，苯妥英钠和卡马西平可能会大大增加心血管和脑血管疾病的风险。《神经病学年鉴》2009;65：448-456
Objective: The widely prescribed anticonvulsants phenytoin and carbamazepine are potent inducers of cytochrome P450 enzymes, which are involved in cholesterol synthesis. We sought to determine whether these drugs have an effect on cholesterol and other serological markers of vascular risk.Methods: We recruited 34 epilepsy patients taking carbamazepine or phenytoin in monotherapy whose physicians had elected to change treatment to one of the noninducing anticonvulsants lamotrigine or levetiracetam. Fasting blood samples were obtained both before and 6 weeks after the switch to measure serum lipid fractions, lipoprotein(a), C-reactive protein, and homocysteine. A comparator group of 16 healthy subjects underwent the same serial studies.Results: In the epilepsy patients, switch from either phenytoin or carbamazepine produced significant declines in total cholesterol (-24.8mg/dl), atherogenic (non-high-density lipoprotein) cholesterol (-19.9mg/dl), triglycerides (-47.lmg/dl) (all p < 0.0001), and C-reactive protein (-31.4%; p = 0.027). Patients who stopped taking carbamazepine also had a 31.2% decline in lipoprotein(a) level (p = 0.0004), whereas those taken off phenytoin had a decrease in homocysteine level (-1.7 mu mol/L; p = 0.005). All of these changes were significant when compared with those seen in healthy subjects (p < 0.05). Results were similar whether patients were switched to lamotrigine or levetiracetam.Interpretation: Switching epilepsy patients from the enzyme-inducers carbamazepine or phenytoin to the noninducing drugs levetiracetam or lamotrigine produces rapid and clinically significant amelioration in several serological markers of vascular risk. These findings suggest that phenytoin and carbamazepine may substantially increase the risk for cardiovascular and cerebrovascular disease. Ann Neurol 2009;65:448-456