Individualized Medicine for Epilepsy -Based on Genetic Information-
Individualized Medicine for Epilepsy -Based on Genetic Information-
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DOI：
10.3805/eands.3.163
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发表时间：
2010
影响因子：
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通讯作者：
Shuichi Yoshida;J. Saruwatari;Lei Chen;Fang Liu;H. Iwasa;Takayuki Sugawara;S. Kaneko
中科院分区：
文献类型：
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作者：
Shuichi Yoshida;J. Saruwatari;Lei Chen;Fang Liu;H. Iwasa;Takayuki Sugawara;S. Kaneko
目前的抗癫痫药物（AED）治疗需要反复试验来确定最有效的AED和剂量，几乎四分之一的患者对AED治疗有抵抗力。基于遗传信息的癫痫个体化治疗是改善目前AED治疗的新途径。然而，在癫痫个体化药物的发展能够进一步进行之前，仍有几个关键问题有待解决。导致常见表型的癫痫基因尚未确定，正在进行的药物遗传学研究继续寻找为什么25%至30%的患者对AED无反应的解释。没有令人信服的临床证据表明P-糖蛋白对临床应答预测的影响。本文就基于基因多态性/突变的癫痫个体化药物开发的现状和前景进行了综述，这些基因多态性/突变与药效学途径、药代动力学途径、对AED特异质反应的预测以及AED的作用机制等核心要素有关。
Current antiepileptic drug (AED) therapy requires trial and error in determining the most effective AED and dosage for a patient, and almost one-fourth of patients are resistant to AED therapy. The introduction of individualized medicine for epilepsy based on genetic information is a new avenue to improve current AED therapy. However, several crucial issues remain to be resolved before the development of individualized medicine for epilepsy can proceed further. The epilepsy genes responsible for common phenotypes have not yet been identified, and ongoing pharmacogenetic studies continue to search for an explanation of why 25 to 30% of patients do not respond to AEDs. There is no convincing clinical evidence indicating the impact of P-glycoprotein on prediction of clinical response. This article provides a critical review of the status and perspectives for the development of individualized medicine for epilepsy based on genetic polymorphisms/mutations in relation to core elements such as pharmacodynamic pathway, pharmacokinetic pathway, prediction of idiosyncratic reaction to AED, and mechanisms of action of AEDs.