Leppik I E
Department of Neurology, University of Minnesota, Minneapolis.
Epilepsia. 1994;35 Suppl 4:S29-40. doi: 10.1111/j.1528-1157.1994.tb05953.x.
Among some 14 new antiepileptic drugs (AEDs), those most extensively tested in humans include felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), vigabatrin (VGB), and zonisamide (ZNS). All are currently marketed in some but not all countries. Although no large, comparative studies on efficacy have been conducted, all of these new AEDs are effective in adult localization-related epilepsies, and some have activity in specific syndromes. Although these drugs all have some CNS side effects, especially when administered in combination with other AEDs, they also all have low toxicity profiles. The availability of AEDs with different mechanisms of action may facilitate rational polytherapy. FBM is not teratogenic in animals. Half-life of FBM in humans is 11-28 h. Daily FBM dosages are 15-45 mg/kg in children and 2,400-4,800 mg in adults. Side effects include insomnia and anorexia, with weight loss. FBM increases phenytoin (PHT) and valproate (VPA) concentrations, and FBM concentration may be affected by other drugs. It is available in the United States for treatment of Lennox-Gastaut syndrome and partial seizures in adults. GBP is very water soluble. Half-life of GBP in humans is 5-7 h and daily dosages range from 900 to 2,400 mg in adults. Few side effects have been observed. GBP is not metabolized by the liver and has no drug interactions. It is available in the United Kingdom and the United States. LTG has no teratogenicity in animal models. Half-life of LTG in humans depends on co-medication: with enzyme inducers it is 15-24 h, and with VPA it is approximately 60 h. LTG dosages are 100-600 mg/day in adults. LTG is available in Europe. OCBZ is rapidly metabolized to 10,11-dihydro-10-hydroxy-carbazepine (MHD), the active compound. Animal studies have shown similar efficacy but superior toxicity to carbamazepine (CBZ) in animal models. For MHD, half-life ranges from 10 to 15 h in patients. OCBZ dosages range from 300 to 1,800 mg/day. VGB is a potent, irreversible inhibitor of GABA transaminase which elevates GABA levels in the CNS. Daily dosages of 2,000-4,000 mg of VGB are needed in adults. Although intramyelinic edema has developed in rats and dogs, it has not yet presented in other mammals or humans. ZNS is a sulfonamide effective in animal models of epilepsy. Half-life of ZNS is 27-36 h. ZNS daily dosage is 400-600 mg. ZNS has been effective in some cases of Baltic myoclonic epilepsy.
在大约14种新型抗癫痫药物（AEDs）中，在人体中进行了最广泛测试的药物包括非氨酯（FBM）、加巴喷丁（GBP）、拉莫三嗪（LTG）、奥卡西平（OCBZ）、氨己烯酸（VGB）和唑尼沙胺（ZNS）。目前，所有这些药物在部分而非所有国家均有上市。尽管尚未开展大规模的疗效对比研究，但所有这些新型AEDs对成人局灶性相关性癫痫均有效，且有些药物在特定综合征中也有活性。尽管这些药物均有一些中枢神经系统副作用，尤其是与其他AEDs联合使用时，但它们的毒性也都较低。作用机制不同的AEDs的可获得性可能有助于合理的联合治疗。FBM在动物中无致畸性。FBM在人体中的半衰期为11 - 28小时。儿童每日FBM剂量为15 - 45mg/kg，成人为2400 - 4800mg。副作用包括失眠和食欲减退，并伴有体重减轻。FBM可提高苯妥英（PHT）和丙戊酸盐（VPA）的浓度，且FBM浓度可能受其他药物影响。在美国，它可用于治疗成人的伦诺克斯 - 加斯东综合征和部分性癫痫发作。GBP极易溶于水。GBP在人体中的半衰期为5 - 7小时，成人每日剂量范围为900至2400mg。观察到的副作用很少。GBP不经肝脏代谢，也无药物相互作用。它在英国和美国均有上市。LTG在动物模型中无致畸性。LTG在人体中的半衰期取决于联合用药：与酶诱导剂合用时为15 - 24小时，与VPA合用时约为60小时。成人LTG剂量为100 - 600mg/天。LTG在欧洲有上市。OCBZ迅速代谢为活性化合物10,11 - 二氢 - 10 - 羟基卡马西平（MHD）。动物研究表明，在动物模型中，其疗效与卡马西平（CBZ）相似，但毒性更低。对于MHD，患者的半衰期为10至15小时。OCBZ剂量范围为300至1800mg/天。VGB是一种强效、不可逆的γ-氨基丁酸转氨酶抑制剂，可提高中枢神经系统中的γ-氨基丁酸水平。成人每日需要2000 - 4000mg的VGB。尽管大鼠和犬类中已出现髓鞘内水肿，但在其他哺乳动物或人类中尚未出现。ZNS是一种在癫痫动物模型中有效的磺胺类药物。ZNS的半衰期为27 - 36小时。ZNS每日剂量为400 - 600mg。ZNS在一些波罗的海肌阵挛性癫痫病例中有效。
