國(guó)際獸醫(yī)癲癇工作組共識(shí)建議：歐洲犬癲癇的藥物治療

Sofie F.M. Bhatti1*, Luisa De Risio2 , Karen Mu?ana3 , Jacques Penderis4 , Veronika M. Stein5 , Andrea Tipold5 , Mette Berendt6 , Robyn G. Farquhar7 , Andrea Fischer8 , Sam Long9 , Wolfgang L?scher10, Paul J.J. Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20?

翻譯 By @蘇蘇蘇蘇喬

校正 By @寵物神經(jīng)科醫(yī)生高健??

Felbamate?非爾氨脂

One veterinary study evaluated the efficacy of felbamate as an adjunct to PB in 6 dogs with focal idiopathic epilepsy [100]. According to Charalambous et al. (2014) [17], the study demonstrated overall moderate/high risk of bias. On this basis it was concluded that there is currently insufficient evidence to recommending the use of felbamate as an add-on AED. Felbamate should be reserved for dogs refractory to the other more thoroughly investigated and safer AEDs in this species and as such this is a 4th or 5th line option. In the clinical study by Ruehlmann et al., (2001) [100] adverse effects noted included keratoconjunctivitis sicca and mild blood dyscrasias (Table 2).

一項(xiàng)獸醫(yī)研究對(duì)6例局灶性特發(fā)性癲癇犬用非爾氨脂作為苯巴比妥輔助藥物的療效進(jìn)行了評(píng)估[100]。Charalambous等（2014）[17]認(rèn)為該研究總體偏倚風(fēng)險(xiǎn)為中/高。在此基礎(chǔ)上得出的結(jié)論是，目前沒(méi)有足夠的證據(jù)建議使用非爾氨脂可以作為輔助抗癲癇藥物。非爾氨脂應(yīng)該保留給對(duì)其他更徹底和更安全的抗癲癇藥物不耐受的犬，因此這是第4或第5線選擇。在Ruehlmann等（2001）[100]的臨床研究中，不良反應(yīng)包括干燥性角膜結(jié)膜炎和輕度血液惡液質(zhì)（表2）。

Felbamate is a dicarbamate AED released for use in humans in 1993 for the control of focal seizures. Its mechanism of action is multiple such as inhibition of glycine-enhanced NMDA-induced intracellular calcium currents [134], blockade of voltage-gated sodium channels and inhibition of voltage –gated calcium currents [133].

非爾氨脂是一種雙氨基甲酸酯抗癲癇藥物（dicarbamate AED），于1993年發(fā)布用于人類，用于控制局灶性抽搐發(fā)作。其作用機(jī)制多種多樣，如，抑制甘氨酸增強(qiáng)的NMDA誘導(dǎo)的細(xì)胞內(nèi)鈣離子電流[134]，阻滯電壓門(mén)控鈉離子通道，和抑制電壓門(mén)控鈣離子電流[133]。

In 1993, felbamate was marketed as a safe AED, which lacked demonstrable toxic side effects and did not require laboratory monitoring in humans. However, within a year of its release it became evident that felbamate was associated with an unacceptable incidence of life-threatening side effects [12], such as anorexia, weight loss, vomiting, headache, irritability. Moreover, aplastic anemia and fatal hepatotoxicity were also described [55, 134].

1993年，非爾氨脂作為一種安全的抗癲癇藥物上市，沒(méi)有明顯的毒副作用，也不需要在人體中進(jìn)行實(shí)驗(yàn)室監(jiān)測(cè)。然而，在其發(fā)布的一年內(nèi)，發(fā)現(xiàn)非爾氨脂與無(wú)法接受的危及生命的副作用的發(fā)生率有明顯相關(guān)[12]，如厭食癥、體重減輕、嘔吐、頭痛、易怒。此外，也有再生障礙性貧血（aplastic anemia）和致死性肝毒性（fatal hepatotoxicity ）的報(bào)道[55,134]。

Pharmacokinetic interactions between felbamate and other AEDs have been well described. E.g. felbamate raises concurrent PB serum levels in a dose-dependent manner [12], and the elimination of felbamate was noted to be strikingly reduced when given with gabapentin [50]. Felbamate is mainly metabolized by the liver [88] and should therefore not be used in dogs with preexisting hepatic disease. Felbamate has an elimination half-life of 5?7h.

非爾氨脂和其他抗癲癇藥物之間的藥代動(dòng)力學(xué)相互作用已有很好描述。例如，非爾氨脂以劑量依賴性的方式提高了血清中同時(shí)存在的苯巴比妥水平[12]，并且當(dāng)與加巴噴丁一起服用時(shí)，非爾氨脂的消除時(shí)間明顯縮短[50]。非爾氨脂主要由肝臟代謝[88]，因此不應(yīng)用于有肝臟病史的犬。非爾氨脂的消除半衰期為5?7小時(shí)。

The recommended oral starting dose in dogs is 20 mg/kg TID, increasing to 400?600mg/day every 1?2 weeks [1]. Haematologic evaluations and biochemistry panels (esp. liver enzyme concentrations) should be performed before felbamate therapy is initiated and during therapy. This is especially important in animals receiving concurrent PB. In humans, the signs of aplastic anaemia and liver failure are usually seen during the first 6?12 months of therapy. In dogs, a minimum of monthly blood tests should be performed for this period of time, following-up every 6?12 months after this. Currently, felbamate is not available in every country.

推薦的犬口服起始劑量為 20 mg/kg TID，每1-2周增加至400-600 mg/天[1]。在非爾氨脂治療開(kāi)始前和治療期間應(yīng)進(jìn)行血液學(xué)評(píng)估和生化檢查（尤其是肝酶濃度）。在同時(shí)使用苯巴比妥的動(dòng)物中尤為重要。在人類中，再生障礙性貧血和肝功能衰竭的癥狀通常在治療的前的6-12個(gè)月出現(xiàn)。在這段時(shí)間內(nèi)，應(yīng)對(duì)犬每月至少一次進(jìn)行血液檢查，此后每6-12個(gè)月復(fù)查一次。目前不是每個(gè)國(guó)家都能買(mǎi)到非爾氨脂。