Adkins J C, Noble S
Adis International Limited, Auckland, New Zealand.
Drugs. 1998 Mar;55(3):437-60. doi: 10.2165/00003495-199855030-00013.
Tiagabine is a gamma-aminobutyric acid (GABA) uptake inhibitor which is structurally related to nipecotic acid but has an improved ability to cross the blood-brain barrier. Clinical trials have shown that tiagabine is effective as add-on therapy in the management of patients with refractory partial epilepsy. In short term studies of this indication, tiagabine < or = 64 mg/day for 7 to 12 weeks reduced the complex partial and simple partial seizure frequency by > or = 50% in 8 to 31 and 28.2 to 37% of patients, respectively. Tiagabine appeared to produce a sustained reduction in seizure frequency in studies of up to 12 months' duration. Data from preliminary studies are currently insufficient to confirm the usefulness of tiagabine when used as monotherapy or in the treatment of children with epilepsy. Further studies are, therefore, necessary to more fully elucidate the efficacy of the drug in these settings. Adverse events associated with tiagabine are primarily CNS-related and include dizziness, asthenia, nonspecific nervousness and tremor. Skin rash or psychosis occurred with similar frequencies among tiagabine- and placebo-treated patients. With long term administration (> or = 1 year for many patients), the profile and incidence of adverse events was similar to that for short term therapy. Tiagabine does not appear to affect the hepatic metabolism of other drugs such as carbamazepine and phenytoin. Possible disadvantages of tiagabine include its short plasma elimination half-life, necessitating 2 to 4 times daily administration, and its inducible hepatic metabolism. Thus, tiagabine is a new antiepileptic agent with a novel mechanism of action, which has demonstrated efficacy in the adjunctive treatment of patients with refractory partial epilepsy. Further investigation of the efficacy of tiagabine is expected to provide a clearer definition of its place in the treatment of epilepsy and its relative merits in relation to other antiepileptic drugs.
噻加宾是一种γ-氨基丁酸（GABA）摄取抑制剂，其结构与哌啶酸相关，但穿越血脑屏障的能力有所提高。临床试验表明，噻加宾作为难治性部分性癫痫患者管理中的附加疗法是有效的。在该适应证的短期研究中，噻加宾≤64mg/天，持续7至12周，分别使8%至31%和28.2%至37%的患者复杂部分性发作和简单部分性发作频率降低≥50%。在长达12个月的研究中，噻加宾似乎能使发作频率持续降低。目前，初步研究数据不足以证实噻加宾作为单一疗法或用于治疗儿童癫痫时的有效性。因此，需要进一步研究以更全面地阐明该药物在这些情况下的疗效。与噻加宾相关的不良事件主要与中枢神经系统有关，包括头晕、乏力、非特异性紧张和震颤。噻加宾治疗组和安慰剂治疗组患者出现皮疹或精神病的频率相似。长期给药（许多患者≥1年）时，不良事件的类型和发生率与短期治疗相似。噻加宾似乎不影响卡马西平和苯妥英等其他药物的肝代谢。噻加宾可能的缺点包括其血浆消除半衰期短，需要每日给药2至4次，以及其可诱导的肝代谢。因此，噻加宾是一种具有新作用机制的新型抗癫痫药物，已在难治性部分性癫痫患者的辅助治疗中显示出疗效。对噻加宾疗效的进一步研究有望更明确其在癫痫治疗中的地位及其与其他抗癫痫药物相比的相对优点。
