國際獸醫(yī)癲癇工作組共識建議：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?

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

盡管唑尼沙胺在日本獲得許可用于治療犬癲癇，但關(guān)于它在犬身上的使用的報道很少。一份報告評估了口服唑尼沙胺作為單藥治療的療效[18]。已有兩項研究評估了唑尼沙胺作為耐藥癲癇犬的輔助治療效果[28,129]?；谶@些研究結(jié)果，Charalambous等人(2014)[17]得出結(jié)論，目前沒有足夠的證據(jù)推薦將唑尼沙胺以單藥治療方式或輔助治療方式用于犬。需要更大規(guī)模的研究來評估唑尼沙胺在犬的單藥療法或作為輔助抗癲癇藥物的效果。犬的不良反應(yīng)包括鎮(zhèn)靜、嘔吐、共濟(jì)失調(diào)和食欲不振[18, 28, 129] （表2）。此外，有2例接受唑尼沙胺單藥治療的犬出現(xiàn)了近期肝毒性，這被認(rèn)為是對該藥物的特質(zhì)性反應(yīng)（idiosyncratic reaction）[69, 104] （表 2）。一例接受唑尼沙胺單藥治療的犬也出現(xiàn)了腎小管酸中毒（Renal tubular acidosis）（表 2）。因此，唑尼沙胺在患有腎臟或肝臟損害的犬中應(yīng)謹(jǐn)慎使用。在接受唑尼沙胺治療的人類群體中也有肝臟和腎臟衰竭的描述。目前，唑尼沙胺并不是在每個國家都能買到，即使能買到，也可能非常昂貴。

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].

唑尼沙胺是一種基于磺酰胺的抗驚厥藥，已獲批準(zhǔn)用于人。確切的藥物作用機(jī)制尚不清楚，然而，阻滯鈣離子通道、增強(qiáng)GABA的釋放、抑制谷氨酸的釋放和抑制電壓門控鈉離子通道，這些可能是其抗驚厥特性的因素[61]。在犬，唑尼沙胺口服后吸收良好，具有相對較長的清除半衰期（約15小時），并且具有低蛋白質(zhì)結(jié)合度，因此藥物相互作用很少。該藥主要通過細(xì)胞色素P450系統(tǒng)進(jìn)行肝臟代謝，然后經(jīng)腎臟排出[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薦起始劑量為3-7mg /kg BID，合并給藥肝微粒體酶誘導(dǎo)劑如苯巴比妥[11,28]的犬的口服佐尼沙胺的起始劑量為7-10mg /kg BID。唑尼沙胺的血清濃度應(yīng)在治療開始或調(diào)整劑量至少1周，血清藥物濃度達(dá)到穩(wěn)定狀態(tài)后測量。采血時應(yīng)注意避免溶血，因為溶解的紅細(xì)胞可能會導(dǎo)致血清唑尼沙胺濃度的假性升高。 人類的10 - 40 mg/L的靶范圍可以作為有效血清藥物濃度的指導(dǎo)[28]。開始唑尼沙胺治療前應(yīng)進(jìn)行基礎(chǔ)全血細(xì)胞計數(shù)和生化檢查，治療期間每6個月檢查一次。