托吡酯(Topiramate)—一种新型抗癫痫药

TOPIRAMATE: A NOVEL ANTIEPILEPTIC DRUG

托吡酯是一种有独特结构，高效的新型抗癫痫药（ＡＥＤ）。托吡酯的抗惊厥机理有三，包括阻滞电压依赖性钠通道，增强γ氨基丁酸（ＧＡＢＡ）活性以及阻滞红藻氨酸谷氨酸受体。托吡酯吸收迅速，为线性药代动力学，在没有肝酶诱导作用ＡＥＤｓ存在的情况下半衰期为２０～３０ｈ。托吡酯不被广泛代谢并由肾脏排出。见于临床对照研究的药物不良反应为轻至中度，主要与中枢神经系统有关，最常见于加量期，尤其是托吡酯剂量增加较快时。综合双盲安慰剂研究的资料表明：托吡酯可使发作显著而有意义的减少，不论其年龄，性别或基础期发作频率有否不同。长期应用托吡酯可保持其控制发作的效果；长期应用托吡酯无耐药性。托吡酯加用治疗难治癫痫发作的初步观察表明对部分性发作以及全身强直阵挛发作的治疗是有希望的。

Topiramte(TPM) is a structurally unique, highly effective new antiepileptic drug(AED). Three mechanisms of action that may contribute to TPM anticonvulsant activity include blockade of voltage-dependent sodium channels, potentiation of gamma aminobutyric acid (GABA) activity, and blockade of kainate glutamate receptors. TPM is rapidly absorbed, and has linear pharmacokinetics, a half-life of 2030 h in the absence of hepatic enzyme inducing AEDs. TPM is not extensively metabolised and is excreted renally. The most common adverse events reported in controlled trials were mild to moderate in severity, mainly CNS related , and occurred most frequently during the titration period when the TPM dosage was rapidly increased. Combined data from double-blind, placebo-controlled trials showed TPM produced statistically significant reductions in seizures regardless of age, gender or baseline seizure frequency. Seizure control appears to be maintained with long-term TPM therapy; no evidence of tolerance wa s seen in patients receiving TPM for long periods. Preliminary finding on TPM as add-on therapy for refractory epileptic seizures including partial seizures and generalized tonic-clonic seizures have seen promising.