Cenobamate is one of the latest antiseizure medications (ASMs) developed for the treatment of focal onset seizures in adult patients. The recommended starting dose is 12.5 mg/day, titrated gradually to the target daily dose of 200 mg, which may be increased to a maximum of 400 mg/day based on clinical response. Although the high rate of seizure freedom observed in randomized, placebo-controlled clinical trials has resulted in exciting expectations, further clinical studies are needed to better define its clinical profile. Cenobamate is characterized by a peculiar pharmacology regarding both pharmacodynamics and pharmacokinetics. The mechanism of action has only partly been described, with the drug acting on voltage-gated sodium channels through a pronounced action on persistent rather than transient currents. Cenobamate also acts as a positive allosteric modulator of GABA_A receptors independently from the benzodiazepine binding site. The bioavailability of cenobamate is not influenced by other drugs, except phenytoin; it can inhibit cytochrome P450 (CYP) 2C19 and induce CYP3A4 and 2B6, and hence can potentially interact with many drugs (e.g. dose adjustments may be required for lamotrigine, carbamazepine and clobazam). The pharmacokinetics of cenobamate are not linear and dosage increases imply a disproportional increase in plasma levels, particularly at doses higher than 300 mg. The most common and dose-related adverse effects associated with cenobamate include central nervous system-related symptoms, mainly somnolence, dizziness, diplopia, and disturbances in gait and coordination. A somewhat higher incidence of adverse events has been observed in patients concomitantly treated with sodium channel blockers. The most relevant safety issues are currently represented by the risk of severe skin reactions (apparently avoidable by a slow titration) and QT shortening (the drug is contraindicated in patients with familial short QT syndrome or taking QT-shortening drugs). Overall, cenobamate is a promising ASM with an intriguing and not fully understood mechanism of action; pharmacokinetic issues need to be considered in clinical practice.

Cenobamate 是最新开发的用于治疗成人患者局灶性癫痫发作的抗癫痫药物 (ASM) 之一。推荐的起始剂量为 12.5 mg/天，逐渐滴定至目标每日剂量 200 mg，根据临床反应可增至最大 400 mg/天。尽管在随机、安慰剂对照的临床试验中观察到的高无癫痫发作率导致了令人兴奋的期望，但仍需要进一步的临床研究来更好地确定其临床特征。Cenobamate 的特征在于药效学和药代动力学方面的特殊药理学。仅部分描述了作用机制，药物通过对持续电流而非瞬态电流的显着作用作用于电压门控钠通道。_一个受体独立于苯二氮卓结合位点。除苯妥英外，cenobamate 的生物利用度不受其他药物的影响；它可以抑制细胞色素 P450 (CYP) 2C19 并诱导 CYP3A4 和 2B6，因此可能与许多药物相互作用（例如，拉莫三嗪、卡马西平和氯巴占可能需要调整剂量）。cenobamate 的药代动力学不是线性的，剂量增加意味着血浆水平的不成比例增加，特别是在剂量高于 300 mg 时。与 cenobamate 相关的最常见和剂量相关的不良反应包括与中枢神经系统相关的症状，主要是嗜睡、头晕、复视以及步态和协调障碍。在同时接受钠通道阻滞剂治疗的患者中观察到不良事件的发生率略高。目前最相关的安全问题是严重皮肤反应的风险（显然可以通过缓慢滴定来避免）和 QT 缩短（该药物禁用于家族性 QT 缩短综合征或服用 QT 缩短药物的患者）。总体而言，cenobamate 是一种很有前途的 ASM，其作用机制引人入胜且尚未完全了解。在临床实践中需要考虑药代动力学问题。