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??

Gabapentin?加巴噴丁

Two prospective studies evaluated the efficacy of oral gabapentin as an adjunct to other AEDs, giving a combined sample size of 28 dogs [44, 89]. According to Charalambous et al. (2014) [17], one study demonstrated an overall moderate/high risk of bias and the other one demonstrated an overall high risk of bias. None of the studies demonstrated an increased likelihood that the majority of the dogs were treated successfully by oral administration of gabapentin. Accordingly, there is currently overall insufficient evidence for recommending the use of gabapentin as an adjunct AED [17]. If used, the recommended oral dosage of gabapentin in dogs is 10 to 20 mg/kg TID, although dose reduction may be necessary in patients with reduced renal function [9]. Sedation and ataxia were the most common side effects reported in dogs [44, 89] (Table 2).

兩項(xiàng)前瞻性研究評(píng)估了口服加巴噴丁作為其他抗抽搐藥輔助藥的療效，共包含28例犬的樣本[44,89]。Charalambous等人（2014）[17]一項(xiàng)研究顯示總體偏倚風(fēng)險(xiǎn)為中/高，另一項(xiàng)研究顯示總體偏倚風(fēng)險(xiǎn)為高。沒有一項(xiàng)研究表明，大多數(shù)犬通過口服加巴噴丁的成功治療的可能性增加。因此，目前推薦加巴噴丁作為輔助抗癲癇藥物的證據(jù)總體不足[17]。如果使用加巴噴丁，推薦犬口服劑量為10-20 mg/kg TID，但腎功能減退的病患可能需要減少劑量[9]。犬中最常見的副作用鎮(zhèn)靜和共濟(jì)失調(diào)44,89。

Gabapentin has been approved in people in Europe and by the US Food and Drug Administration (FDA) since 1993 for adjunctive treatment of focal seizures with or without secondary generalisation and for the treatment of post-herpetic neuralgia [9]. Its precise mechanism of action is unclear, but is believed that much of its anticonvulsant effect is because of its binding to a specific modulatory protein of voltage-gated calcium channels, which results in decreased release of excitatory neurotransmitters [112]. In humans, gabapentin is entirely excreted by the kidneys. In dogs, renal excretion occurs after a partial hepatic metabolism. The elimination half-life is 3?4h.

自1993年以來，加巴噴丁已獲得歐洲和美國(guó)食品和藥物管理局（FDA）的批準(zhǔn)用于伴有或不伴有繼發(fā)性全身發(fā)作的局灶性抽搐發(fā)作的輔助治療以及皰疹后神經(jīng)痛的治療[9]。其確切的作用機(jī)制尚不清楚，但一般認(rèn)為其抗驚厥作用主要是由于其與電壓門控鈣離子通道的特定調(diào)節(jié)蛋白結(jié)合，導(dǎo)致興奮性神經(jīng)遞質(zhì)的釋放減少[112]。在人類中，加巴噴丁完全由腎臟排出。在犬，腎臟排泄發(fā)生在部分性肝臟代謝之后。清除半衰期為3?4小時(shí)。

Although information in veterinary medicine is limited, pharmacokinetic interactions of gabapentin are unlikely to occur as the drug has negligible protein binding and does not induce hepatic cytochrome P450 family enzymes [95]. In humans, the elimination of felbamate was noted to be significantly reduced when given with gabapentin [50]. The most common adverse effects in humans include dizziness, somnolence and fatigue [9]. These effects seem to be dose-dependent and resolve within the first few weeks of treatment. No serious idiosyncratic reactions or organ toxicities have been identified in humans or animals [60].

雖然獸醫(yī)醫(yī)學(xué)方面的信息有限，但加巴噴丁的藥代動(dòng)力學(xué)相互作用不太可能發(fā)生，因?yàn)樵撍幬锏牡鞍踪|(zhì)結(jié)合可以忽略不計(jì)，并且不會(huì)誘導(dǎo)肝細(xì)胞色素P450族酶[95]。在人類中，加巴噴丁可顯著降低非氨酯的清除[50]。人類最常見的不良反應(yīng)包括頭暈、嗜睡和疲勞[9]。這些影響似乎是劑量依賴性的，并在治療的最初幾周內(nèi)消退。在人類或動(dòng)物中未發(fā)現(xiàn)嚴(yán)重的特質(zhì)性反應(yīng)（idiosyncratic reactions）或器官毒性[60]。