国际兽医癫痫工作组共识建议：欧洲犬癫痫的药物治疗

Sofie F.M. Bhatti1*, Luisa De Risio2 , Karen Muñana3 , Jacques Penderis4 , Veronika M. Stein5 , Andrea Tipold5 , Mette Berendt6 , Robyn G. Farquhar7 , Andrea Fischer8 , Sam Long9 , Wolfgang Löscher10, Paul J.J. Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20 

翻译 By @苏苏苏苏乔

校正 By @宠物神经科医生高健 

Zonisamide 唑尼沙胺

There are few reports on the use of zonisamide in dogs, despite it being licensed for treatment of canine epilepsy in Japan. One report evaluated the efficacy of oral zonisamide as a monotherapy [18]. Two studies have been described evaluating zonisamide as an add-on treatment in dogs with drug resistant epilepsy [28, 129]. Based on the results of these studies, Charalambous et al. (2014) [17] concluded that, at present, there is insufficient evidence to recommend the use of zonisamide either as a monotherapy or as an adjunct AED in dogs. Larger studies are required to evaluate zonisamide as a monotherapy or as an adjunctive AED in dogs. Adverse effects in dogs include sedation, vomiting, ataxia, and loss of appetite [18, 28, 129] (Table 2). Additionally, recently hepatotoxicity has been described in 2 dogs receiving zonisamide monotherapy which is believed to be an idiosyncratic reaction to the drug [69, 104] (Table 2). Renal tubular acidosis has also been described in a dog receiving zonisamide monotherapy [20] (Table 2). Thus, zonisamide should be used with caution in dogs with renal or hepatic impairment. Both, hepatic and renal failures have been described in humans receiving zonisamide as well. Currently, zonisamide is not available in every country and when available, it can be very expensive

尽管唑尼沙胺在日本获得许可用于治疗犬癫痫，但关于它在犬身上的使用的报道很少。一份报告评估了口服唑尼沙胺作为单药治疗的疗效[18]。已有两项研究评估了唑尼沙胺作为耐药癫痫犬的辅助治疗效果[28,129]。基于这些研究结果，Charalambous等人(2014)[17]得出结论，目前没有足够的证据推荐将唑尼沙胺以单药治疗方式或辅助治疗方式用于犬。需要更大规模的研究来评估唑尼沙胺在犬的单药疗法或作为辅助抗癫痫药物的效果。犬的不良反应包括镇静、呕吐、共济失调和食欲不振[18, 28, 129] （表2）。此外，有2例接受唑尼沙胺单药治疗的犬出现了近期肝毒性，这被认为是对该药物的特质性反应（idiosyncratic reaction）[69, 104] （表 2）。一例接受唑尼沙胺单药治疗的犬也出现了肾小管酸中毒（Renal tubular acidosis）（表 2）。因此，唑尼沙胺在患有肾脏或肝脏损害的犬中应谨慎使用。在接受唑尼沙胺治疗的人类群体中也有肝脏和肾脏衰竭的描述。目前，唑尼沙胺并不是在每个国家都能买到，即使能买到，也可能非常昂贵。

Zonisamide is a sulphonamide-based anticonvulsant approved for use in humans. The exact mechanism of action is unknown, however, blockage of calcium channels, enhancement of GABA release, inhibition of glutamate release, and inhibition of voltage-gated sodium channels might contribute to its anticonvulsant properties [61]. In dogs, zonisamide is well-absorbed after oral administration, has a relatively long elimination half-life (approximately 15h), and has low protein binding so that drug interactions are minimized. The drug mainly undergoes hepatic metabolism via the cytochrome P450 system before excretion by the kidneys [11].

唑尼沙胺是一种基于磺酰胺的抗惊厥药，已获批准用于人。确切的药物作用机制尚不清楚，然而，阻滞钙离子通道、增强GABA的释放、抑制谷氨酸的释放和抑制电压门控钠离子通道，这些可能是其抗惊厥特性的因素[61]。在犬，唑尼沙胺口服后吸收良好，具有相对较长的清除半衰期（约15小时），并且具有低蛋白质结合度，因此药物相互作用很少。该药主要通过细胞色素P450系统进行肝脏代谢，然后经肾脏排出[11]。

The recommended oral starting dose of zonisamide in dogs is 3−7 mg/kg BID and 7−10 mg/kg BID in dogs coadministered hepatic microsomal enzymes inducers such as PB [11, 28]. Serum concentrations of zonisamide should be measured minimally 1 week after treatment initiation or dosage adjustment to allow steady state concentrations be reached. Care should be taken to avoid haemolysis, as falsely elevated serum zonisamide concentrations from lysed red blood cells may occur. The human target range of 10−40 mg/l can be used as guidance regarding effective concentrations. [28]. Baseline complete blood cell count and biochemical profile should be performed before starting zonisamide treatment and periodically every 6 months during treatment.

犬口服唑尼沙胺的推荐起始剂量为3-7mg /kg BID，合并给药肝微粒体酶诱导剂如苯巴比妥[11,28]的犬的口服佐尼沙胺的起始剂量为7-10mg /kg BID。唑尼沙胺的血清浓度应在治疗开始或调整剂量至少1周，血清药物浓度达到稳定状态后测量。采血时应注意避免溶血，因为溶解的红细胞可能会导致血清唑尼沙胺浓度的假性升高。 人类的10 - 40 mg/L的靶范围可以作为有效血清药物浓度的指导[28]。开始唑尼沙胺治疗前应进行基础全血细胞计数和生化检查，治疗期间每6个月检查一次。