International Veterinary Epilepsy Task Forceによるコンセンサス提案 ...

1 1 BMC Veterinary Research (2015) 11:176 DOI International Veterinary Epilepsy Task Force [ International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine Epilepsy in Europe] Sofie 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 Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20 Background antiepileptic drugs AEDs 1 2 3 4 AED AED 1 [17] 2 3 Abstract AEDs 1 2 3 4 AED AED 1 2 3 AEDs Keywords 2 AEDs AEDs AEDs AED anti-seizure drugs , AED [63]

2 >2% / Aims of AED treatment AED AED QOL QOL AED [23,76,91,92,120] AED AED AED AED When to recommend maintenance AED treatment? AED AED 6 6 2 24 / / 3 AED [42 115] AED [42] [43,108] AED [12-14] 6 10 [132] AED [84] AED AED [16,34,59] kindling [117]

3 [54] [111] multifactorial pathogenesis [14,52] 3 AEDs [99] [132] [49,84] [24] [84] [77] [7] [45] [3,77] Choice of AED therapy AED AEDs AED AED [23] AED phenobarbital PB potassium bromide KBr AEDs AEDs add-on treatment 2013 imepitoin AEDs phenytoin carbamazepine valproic acid ethosuximide [119] lamotrigine [26,136] vigabatrin [113 131 138] 1990 AEDs levetiracetam zonisamide felbamate topiramate gabapentin pregabalin lacosamide[68] rufinamide[137]

4 Phenobarbital PB AED 2009 PB [2 87 97] PB 25 35 mg/l g/ml 60 93% [10,31,74,105] Charalambous et al. 2014 [17] monotherapy AED PB PB PB Br AED PB 85% 6 seizure-free Br 52% [10] Br PB PB 2 90% [2 87] 4 8 [2,97] 37 73 [96] 45% [36] PB PB 4 25% PB [2,87,97] PB P450 [48] [107] PB P450 metabolic tolerance autoinduction [40 48] PB 30 45 [97]

5 PB PB PB IM IV PB IM IV PB PB IM PB IM [135] IV 93 [87] PB P450 , / [48] PB AEDs [23,33,72,82,130] PB [130] PB P450 PB [10] PB [35,121] Table 1 PB [23,32,91] [13,22,39,75] / / [51,56] [66] [38,46] [58] [58] [41] Table 1 PB [23,32,91] PB [39,41,75] [41] - [21,41,128] [23,32,91] Fig 1 PB 3 mg/kg BID PB 14 6 2 PB PB [23]

6 Steady-state PB [62,70] 5 mg/kg BID trough concentration 5 PB [70] PB PB [10] PB therapeutic range 15 mg/l 40 mg/l 25 30 mg/l PB 35 mg/l [22,75] PB A PB mg PB PB PB mg AED 50% [23] PB loading dose 15 20 mg/kg 24 48 3 5 mg/kg IV IM PO [10] PB 1 3 40 60 10 12 mg/kg IV 20 4-6 mg/kg 2 PB 3 6 PB 6 12 Imepitoin AED [102] 2013 [64,98,122] [30] [122] 226 PB 10 20 30 mg/kg 2 PB PB [122] Rieck et al 2006 [98] PB primidone AED KBr Charalambous et al 2014 [17]

7 AED AED AED PB PB combined therapy PB Fig. 2 30 mg/kg 30 2 3h [101] 2h 6h BID [64] AEDs [122] 6 1 2 [64,122] GABAA [122] GABAA [122] AED PB Table1 10 30 mg/kg BID [64,98] [96]

8 6 150 mg/kg q12h CNS 24h AED 1 2 [96] 5 kg [96] GABAA tolerance dependence [122] withdrawal signs [64] Fig. 2 10 30 mg/kg BID 10 20 mg/kg BID 1 30 mg/kg BID [64] therapeutic index 6 12 Bromide Br KBr NaBr Br KBr 15% [124] EU KBr AED PB KBr synergistic effect KBr PB [46,93,126] KBr PB [10] Charalambous et al 2014 [17]

9 KBr AED Br 46% 25 46 3 [46,67,90,125] KBr 7 KBr KBr KBr [123] KBr KBr KBr 5 KBr pseudohyperchloraemia [123] KBr KBr KBr KBr KBr KBr KBr [80] KBr / [4,25,46,124] Table 1 PB KBr [125] Br 1 2 [4] KBr [4,46,67,106] Table 1 KBr bromoderma [106] Br [23,32,91] Fig.

10 3 KBr 15 mg/kg BID 20 mg/kg BI