PDF(Pubmed)
Abstract：
Drug-resistant epilepsy is a common complaint in dogs and affects up to 30% of dogs with idiopathic epilepsy. Experimental data suggest that targeting cyclooxygenase-2 (COX-2) mediated signaling might limit excessive excitability and prevent ictogenesis. Moreover, the role of COX-2 signaling in the seizure-associated induction of P-glycoprotein has been described. Thus, targeting this pathway may improve seizure control based on disease-modifying effects as well as enhancement of brain access and efficacy of the co-administered antiseizure medication. The present open-label non-controlled pilot study investigated the efficacy and tolerability of a COX-2 inhibitor (firocoxib) add-on therapy in a translational natural occurring chronic epilepsy animal model (client-owned dogs with phenobarbital-resistant idiopathic epilepsy). The study cohort was characterized by frequent tonic-clonic seizures and cluster seizures despite adequate phenobarbital treatment. Enrolled dogs (n = 17) received a firocoxib add-on therapy for 6 months. Tonic-clonic seizure and cluster seizure frequencies were analyzed at baseline (6 months) months during the study (6 months). The responders were defined by a substantial reduction of tonic-clonic seizure and cluster seizure frequency (≥50%). In total, eleven dogs completed the study and were considered for the statistical analysis. Two dogs (18%, 2/11) were classified as responders based on their change in seizure frequency. Interestingly, those two dogs had the highest baseline seizure frequency. The overall tolerability was good. However, given the low percentage of responders, the present data do not support an overall considerable efficacy of COX-2 inhibitor add-on therapy to overcome naturally occurring phenobarbital-resistant epilepsy in dogs. Further translational evaluation should only be considered in the canine patients with a very high baseline seizure density.
摘要：
抗药性癫痫是狗的常见主诉，影响多达30％的特发性癫痫犬。实验数据表明，靶向环加氧酶-2（COX-2）介导的信号传导可能会限制过度的兴奋性并防止发生。此外，已经描述了COX-2信号在癫痫发作相关的P-糖蛋白诱导中的作用。因此，靶向这一途径可能会改善癫痫发作的控制,这主要是基于疾病的改善作用,以及增强脑通路和共同给药的抗癫痫药物的疗效.目前的开放标签非对照试点研究调查了COX-2抑制剂（firocoxib）附加疗法在转化自然发生的慢性癫痫动物模型（客户拥有的狗患有苯巴比妥抗性特发性癫痫）中的疗效和耐受性。尽管有足够的苯巴比妥治疗，但该研究队列的特征是频繁的强直阵挛性癫痫发作和集束性癫痫发作。登记的狗(n=17)接受费罗昔布附加疗法6个月。在研究期间（6个月）的基线（6个月）分析了强直阵挛性癫痫发作和集群性癫痫发作频率。反应者的定义是强直阵挛性癫痫发作和集束性癫痫发作频率的显着降低（≥50％）。总的来说,11只狗完成了研究，并考虑进行统计分析。两只狗（18%，2/11）根据癫痫发作频率的变化将其分类为响应者。有趣的是,这两只狗的基线癫痫发作频率最高。总体耐受性良好。然而,鉴于响应者的比例较低，目前的数据不支持COX-2抑制剂附加疗法在克服犬中自然发生的苯巴比妥耐药癫痫方面的总体疗效相当.仅应在基线癫痫发作密度非常高的犬科患者中考虑进一步的转化评估。
