Department of Pharmacy, Faculty of Health Sciences, Oslo University College, Oslo, Norway.
Expert Rev Neurother. 2010 Jan;10(1):119-40. doi: 10.1586/ern.09.136.
During the period 1989-2009, 14 new antiepileptic drugs (AEDs) were licensed for clinical use and these can be subdivided into new second- and third-generation AEDs. The second-generation AEDs comprise felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. The third-generation AEDs comprise eslicarbazepine acetate and lacosamide. The interaction propensity of AEDs is very important because all new AEDs are licensed, at least in the first instance, as adjunctive therapy. The present review summarizes the interactions (pharmacokinetic and pharmacodynamic) that have been reported with the newer AEDs. The pharmacokinetic interactions include those relating to protein-binding displacement from albumin in blood, and metabolic inhibitory and induction interactions occurring in the liver. Overall, the newer AEDs are less interacting because their pharmacokinetics are more favorable and many are minimally or not bound to blood albumin (e.g., eslicarbazepine, felbamate, gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) and are primarily renally excreted or metabolized by noncytochrome P450 or uridine glucoronyl transferases (e.g., gabapentin, lacosamide levetiracetam, rufinamide, topiramate and vigabatrin) as opposed to hepatic metabolism which is particularly amenable to interference. Gabapentin, lacosamide, levetiracetam, pregabalin and vigabatrin are essentially not associated with clinically significant pharmacokinetic interactions. Of the new AEDs, lamotrigine and topiramate are the most interacting. Furthermore, the metabolism of lamotrigine is susceptible to both enzyme inhibition and enzyme induction. While the metabolism of felbamate, tiagabine, topiramate and zonisamide can be induced by enzyme-inducing AEDs, they are less vulnerable to inhibition by valproate. Noteworthy is the fact that only five new AEDs (eslicarbazepine, felbamate, oxcarbazepine, rufinamide and topiramate) interact with oral contraceptives and compromise contraception control. The most clinically significant pharmacodynamic interaction is that relating to the synergism of valproate and lamotrigine for complex partial seizures. Compared with the first-generation AEDs, the new second- and third-generation AEDs are less interacting, and this is a desirable development because it allows ease of prescribing by the physician and less complicated therapeutic outcomes and complications for patients.
在 1989 年至 2009 年期间，有 14 种新的抗癫痫药物（AED）获得了临床使用许可，这些药物可进一步分为第二代和第三代 AED。第二代 AED 包括苯妥英、加巴喷丁、拉莫三嗪、左乙拉西坦、奥卡西平、普瑞巴林、鲁非酰胺、司替戊醇、噻加宾、托吡酯、氨己烯酸和唑尼沙胺。第三代 AED 包括乙琥胺和拉科酰胺。AED 的相互作用倾向非常重要，因为所有新的 AED 至少在最初阶段都被许可作为辅助治疗药物。本综述总结了与新型 AED 相关的（药代动力学和药效动力学）相互作用。药代动力学相互作用包括与血液白蛋白结合的蛋白置换相关的相互作用，以及发生在肝脏中的代谢抑制和诱导相互作用。总的来说，新型 AED 的相互作用较少，因为它们的药代动力学更有利，许多药物与血液白蛋白的结合较少或不结合（例如，乙琥胺、苯妥英、加巴喷丁、拉科酰胺、左乙拉西坦、鲁非酰胺、托吡酯和氨己烯酸），并且主要通过肾脏排泄或非细胞色素 P450 或尿苷葡萄糖醛酸转移酶代谢（例如，加巴喷丁、拉科酰胺、左乙拉西坦、鲁非酰胺、托吡酯和氨己烯酸），而不是肝脏代谢，这尤其容易受到干扰。加巴喷丁、拉科酰胺、左乙拉西坦、普瑞巴林和氨己烯酸基本上与临床相关的药代动力学相互作用无关。在新型 AED 中，拉莫三嗪和托吡酯的相互作用最大。此外，拉莫三嗪的代谢易受到酶抑制和酶诱导的影响。虽然苯妥英、噻加宾、托吡酯和唑尼沙胺的代谢可以被酶诱导的 AED 诱导，但它们对丙戊酸的抑制作用不太敏感。值得注意的是，只有五种新型 AED（乙琥胺、苯妥英、奥卡西平、鲁非酰胺和托吡酯）与口服避孕药相互作用，从而影响避孕效果。最具临床意义的药效动力学相互作用是丙戊酸和拉莫三嗪对复杂部分性发作的协同作用。与第一代 AED 相比，新型第二代和第三代 AED 的相互作用较小，这是一个理想的发展，因为它允许医生轻松开处方，为患者提供更简单的治疗效果和并发症。
