Немного попробовал разобраться в вопросе. Мда… собаки немного не люди. Более или менее понятно стало.
Вальпроаты собакам не подходят, все перепробовано. У собак эффект имеют только фенобарбитураты.
Все ПЭП обкатывают на животных и все эффекты прослеживаются. Вот не верю, что прямо совсем ничего не работает, только барбитура. Может у одной конкретной собаки быть ответ на один ПЭП много выше, но чтобы вот нифига - не верю. Все работает, проблема в метаболизме - низкий период полувыведения - необходимость частого и сверхчастого дозирования для создания концентрации и контроля судорог. И тут - да, в итоге основная масса ПЭП, видимо, не применима во вменяемых режимах. Но вот статус снимать парентеральными формами вальпроатов, думаю, можно и попробовать, хотя, уверен, по этому поводу есть работы, стоит поискать. Может и не прав и там какой подводный камень.
Для инфы о форме: Конвулекс р-р д/ин в/в 100мг/мл амп 5мл\N5 АВС Герот\ примерно от 1000 р за 5 ампул.
По дозировке я затрудняюсь, человеку я дал бы от 1,5-5 мг/кг/мин суммарной дозой до 45 мг/кг. Собаки… наверное, можно и больше, с учетом быстрого метаболизма.
В принципе риски мизерные, во всяком случае куда ниже, чем по релахе, которая может дыхание стопануть, у человека это не самое веселое, что бывает, а как раздышать собаку…
Valproic Acid
This medication is effective in humans with all types of seizures; however, it is metabolized very quickly in dogs and therefore its use is limited. Valproic Acid is primarily used in combination with other drugs such as Phenobarbital. Potential side effects include loss of hair and liver disease.
Written by Dr. William Thomas, DVM, MS on Valproic Acid:
Valproate (valproic acid, Depekene) is considered a second line drug for the treatment of epilepsy in dogs. The elimination half-life in dogs is fairly short (approximately 3 hours) compared to people (5 to 15 hours). Thus, unless very high doses are used, blood levels of valproate in dogs are less than concentrations known to be therapeutic in people. However, these blood levels may still be sufficient in dogs, since lower protein binding of valproate in dogs gives rise to higher brain concentrations,
compared to people.
In one short-term study, treatment with valproate alone was effective in reducing seizure frequency by 50% or more in 7 out of 16 dogs (44%) with idiopathic epilepsy. When used in conjunction with other anti-seizure drugs (mostly phenobarbital or primidone), valproate was successful in reducing seizure frequency by at least 50% in 21 of 41 dogs (51%). Because of the lack of long term studies and concerns about the rapid metabolism in dogs, valproate is currently considered a second line drug for the treatment of canine epilepsy. It is used primarily in dogs whose seizures are not well controlled with phenobarbital or bromide.
Side effects:
Nausea and vomiting. These can usually be avoided by giving valproate with or soon after meals.
Drowsiness and sedation can occur, especially at higher doses or when valproate is combined with other antiseizure drugs.
Hair loss has been observed in dogs and people.
Liver disease has been reported in about 1 in 3700 people (1 in 500 young children) treated with valproate. Although valproate-induced liver disease has not been documented in dogs, there are no large, long-term studies of this drug in dogs with epilepsy.
Loscher W. Plasma levels of valproic acid and its metabolites during
continued treatment in dogs. Journal of Veterinary Pharmacology and
Therapeutics 4:111-119,1981.
Nafe LA. Sodium valproate: A preliminary clinical trial in epileptic dogs
Journal of the American Animal Hospital Association17:131-133,1981.
WB Thomas DVM,MS
Dipl.ACVIM(Neurology)
University of Tennessee
Да, слишком низкий T1/2
И то… в исследовании 50% дали ответ. Возможная тактика - частый прием препарата (скажем уже при 4 кратном приеме концентрации должны держаться) и выбор максимально пролонгированных форм, это, конечно, может быть технически сложно, но все же…
Keppra (Levetiracetam)
Written by Dr. William Thomas, DVM, MS
Keppra (levetiracetam) is approved in the US for people with focal seizures refractory to other anti-seizure drugs. I’m not aware of any clinical or long-term safety studies in dogs. The elimination half-life in dogs is about 3.6 hours. This compares to 7-10 hours in people.
I have used it in a few dogs with epilepsy refractory to other medication, but experience is still too limited to tell if this will prove to be a useful drug for dogs.
WB Thomas DVM,MS
Dipl.ACVIM(Neurology)
University of Tennessee
Используют, при резистентности к барбитуре, видимо, хотя о выводах четко говорить не хотят пока.
Опять же для резистентных пишут про калия бромид, и комбинацию с барбитурой, и его думаю достать не сложно.
Potassium bromide (KBr) is gaining new recognition for use in refractory (difficult to control) canine epilepsy, though used to treat human epileptics as early as 1857. It is the anticonvulsant of choice for dogs with liver disease. Sodium bromide is preferred for dogs with kidney problems. Combining potassium bromide or sodium bromide and phenobarbitol may be useful for patients who do not respond well to phenobarbital or primidone alone.
Про зонегран пишут, 10 мг/кг 2 раза в сутки, но в РФ его не достать, хотя мои двуногие таскают из ЕС для себя вполне, значит, не невозможно.
Про Клоразепат пишут, но в РФ его днем с огнем… опять же..
Clorazepate (Tranxene)
Written by Dr. William Thomas, DVM, MS
Clorazepate (Tranxene) was introduced in the United States in 1981. It is used mostly as add-on therapy in people. It is sometimes used as add-on therapy in dogs unresponsive to first line drugs.
After oral administration, clorazepate is converted to nordiazepam (also called N-desmethyldiazepam), in the stomach. Nordiazepam provides all of the antiseizure effect. The elimination half-life is 2 to 5 hours, tending to be slightly longer with long term administration. A dose of 2 mg/kg every 8 or 12 hours has been suggested.
Sustained release tablets (Tranxene SD) offer no pharmacokinetic advantages over regular-release tablets in dogs. Coadministration of phenobarbital with clorazepate results in lowered blood levels of clorazepate. Tolerance (reduction in anti-seizure effects with long-term use) can occur with clorazepate, as with most other benzodiazepines.
Forrester SD, et al. Disposition of clorazepate in dogs after single- and
multiple-dose oral administration. American Journal of Veterinary Research
51:2001-2005,1990.
Brown SA, Forrester SD. Serum disposition of oral clorazepate from
regular-release and sustained-delivery tablets in dogs. Journal of
Veterinary Pharmacology and Therapeutics. 14:426-429,1991.
Forrester SD, et al. Effects of a 44-day administration of phenobarbital on
disposition of clorazepate in dogs. American Journal of Veterinary Research
54:1136-1138,1993.
Scherkl R, et al. Clorazepate in dogs: tolerance to the anticonvulsant
effect and signs of physical dependence. Epilepsy Research 3:144-150,1989.