Rundfeldt Chris, Tipold Andrea, Löscher Wolfgang
Drug-Consulting Network, 01445, Coswig, Germany.
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.
BMC Vet Res. 2015 Sep 2;11:228. doi: 10.1186/s12917-015-0548-9.
Imepitoin is a novel antiepileptic drug for the treatment of canine idiopathic epilepsy. The present study was conducted to demonstrate superior antiepileptic activity of a high dose of 30 mg/kg BID over a low dose of 1 mg/kg BID of imepitoin during 12 weeks of treatment under double blind conditions in a field population of dogs with previously untreated epilepsy. In a consecutive 12 weeks open label follow up (phase 2), all animals received 30 mg/kg BID, to evaluate the persistence of the antiepileptic activity, and to evaluate the effect of a dose step up to 30 mg/kg in the former low-dose animals.
A treatment with 30 mg/kg BID resulted in a significantly greater reduction in monthly seizure frequency relative to baseline data as compared to the 1 mg/kg dose. Both generalized and partial seizures but not cluster seizures were significantly less frequent in the high dose group. The antiepileptic activity was maintained during study phase 2 in the high dose group. An increase to 30 mg/kg BID in the low- dose animals resulted in a significant reduction in generalized and partial seizures, but not cluster seizures. At the end of study phase 2, 32.1 and 46.8 % of dogs of the former high and former low-dose groups respectively, remained free of generalized tonic-clonic seizures. Imepitoin was well tolerated. The frequency of dogs with any adverse drug reactions was higher in the 30 mg/kg BID dose (59 % vs. 41 %, p = 0.041), and the main target organ was the central nervous system (CNS). The occurrence of CNS related adverse reactions was transient and findings were mostly restricted to the first weeks of treatment. No hepatic enzyme increase and no other organ toxicity were observed.
The administration of imepitoin twice daily at a dose of 30 mg/kg results in significant and persistent antiepileptic effects in patients with newly diagnosed epilepsy and generalized tonic-clonic seizures, as observed over a study period of up to 6 months. Imepitoin was well tolerated. Most CNS related adverse drug reactions were transient. Both the antiepileptic activity and the safety profile make the drug suitable for long-term clinical use.
艾美嘧啶是一种用于治疗犬特发性癫痫的新型抗癫痫药物。本研究旨在证明，在双盲条件下，对先前未经治疗的癫痫犬群进行为期12周的治疗期间，高剂量30毫克/千克每日两次比低剂量1毫克/千克每日两次的艾美嘧啶具有更强的抗癫痫活性。在连续12周的开放标签随访（第二阶段）中，所有动物均接受30毫克/千克每日两次的治疗，以评估抗癫痫活性的持续性，并评估在先前低剂量动物中剂量增加至30毫克/千克的效果。
与1毫克/千克剂量相比，30毫克/千克每日两次的治疗使每月癫痫发作频率相对于基线数据显著降低。高剂量组全身发作和部分性发作的频率均显著降低，但丛集性发作并非如此。在研究的第二阶段，高剂量组的抗癫痫活性得以维持。低剂量动物剂量增加至30毫克/千克每日两次后全身发作和部分性发作显著减少，但丛集性发作并非如此。在研究第二阶段结束时，先前高剂量组和低剂量组分别有32.1%和46.8%的犬未出现全身强直阵挛性发作。艾美嘧啶耐受性良好。30毫克/千克每日两次剂量组出现任何药物不良反应的犬的频率更高（59%对41%，p = 0.041），主要靶器官是中枢神经系统（CNS）。CNS相关不良反应的发生是短暂的，且发现大多局限于治疗的最初几周。未观察到肝酶升高及其他器官毒性。
在长达6个月的研究期间观察到，对于新诊断的癫痫和全身强直阵挛性发作患者，每日两次给予30毫克/千克剂量的艾美嘧啶可产生显著且持续的抗癫痫作用。艾美嘧啶耐受性良好。大多数CNS相关药物不良反应是短暂的。抗癫痫活性和安全性均使该药物适合长期临床使用。
