Effects of antiepileptic drugs on lipids, homocysteine, and C‐reactive protein

拉莫三嗪 苯妥英钠 卡马西平 左乙拉西坦 癫痫 医学 药理学 抗惊厥药 同型半胱氨酸 内科学 内分泌学 精神科
作者
Scott Mintzer,Christopher Skidmore,Caitlin J. Abidin,Megan C. Morales,Inna Chervoneva,David M. Capuzzi,Michael R. Sperling
出处
期刊:Annals of Neurology [Wiley]
卷期号:65 (4): 448-456 被引量:204
标识
DOI:10.1002/ana.21615
摘要

Abstract 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 (−47.1mg/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 (−1.7μmol/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
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