Tolerability and pharmacokinetics of intravenous allopregnanolone with and without midazolam pretreatment in two healthy dogs

Bruun, Donald A.; Ma, Betty; Chen, Yi‐Je; Wu, Chun‐Yi; Aleman, Monica R; Żółkowska, Dorota; Smiley‐Jewell, Suzette; Rogawski, Michael A.; Lein, Pamela J.

doi:10.1002/epi4.12723

Cited by 2 publications

(2 citation statements)

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“…In veterinary medicine, evidence and clinical experience are limited to absent. 68 , 111 , 174 Pharmacological interventions such as IV magnesium 68 and allopregnanolone, 85 , 111 as well as mild hypothermia 53 might provide further antiseizure effects in dogs and cats with super‐refractory SE.…”

Section: What If the Combined Measures With First‐ Second‐ And Third‐...mentioning

confidence: 99%

“… 176 Two pharmacokinetic studies in dogs showed a favorable pharmacokinetic and safety profile for allopregnanolone in SE. 85 , 111 Hypothermia decreases excitatory neurotransmitters, calcium‐ and glutamate‐induced excitotoxicity, and cerebral metabolic rate, and normalizes intracranial pressure. 177 , 178 According to a clinical report in dogs, 53 mild hypothermia (36.7‐37.7°C) when combined with ketamine‐dexmedetomidine IV CRI was effective in terminating super‐refractory SE.…”

Section: What If the Combined Measures With First‐ Second‐ And Third‐...mentioning

confidence: 99%

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ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats

Charalambous,

Muñana,

Patterson

et al. 2023

Veterinary Internal Medicne

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BackgroundSeizure emergencies (ie, status epilepticus [SE] and cluster seizures [CS]), are common challenging disorders with complex pathophysiology, rapidly progressive drug‐resistant and self‐sustaining character, and high morbidity and mortality. Current treatment approaches are characterized by considerable variations, but official guidelines are lacking.ObjectivesTo establish evidence‐based guidelines and an agreement among board‐certified specialists for the appropriate management of SE and CS in dogs and cats.AnimalsNone.Materials and MethodsA panel of 5 specialists was formed to assess and summarize evidence in the peer‐reviewed literature with the aim to establish consensus clinical recommendations. Evidence from veterinary pharmacokinetic studies, basic research, and human medicine also was used to support the panel's recommendations, especially for the interventions where veterinary clinical evidence was lacking.ResultsThe majority of the evidence was on the first‐line management (ie, benzodiazepines and their various administration routes) in both species. Overall, there was less evidence available on the management of emergency seizure disorders in cats in contrast to dogs. Most recommendations made by the panel were supported by a combination of a moderate level of veterinary clinical evidence and pharmacokinetic data as well as studies in humans and basic research studies.Conclusions and Clinical RelevanceSuccessful management of seizure emergencies should include an early, rapid, and stage‐based treatment approach consisting of interventions with moderate to preferably high ACVIM recommendations; management of complications and underlying causes related to seizure emergencies should accompany antiseizure medications.

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Section: What If the Combined Measures With First‐ Second‐ And Third‐...mentioning

confidence: 99%

Section: What If the Combined Measures With First‐ Second‐ And Third‐...mentioning

confidence: 99%

ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats

Charalambous,

Muñana,

Patterson

et al. 2023

Veterinary Internal Medicne

View full text Add to dashboard Cite

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Tolerability and pharmacokinetics of intravenous allopregnanolone with and without midazolam pretreatment in two healthy dogs

Bruun

Chen

et al. 2023

Epilepsia Open

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The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine-refractory status epilepticus (SE). Here we assess the cardiopulmonary safety of intravenous ALLO by itself and after a clinically recommended dose of midazolam (MDZ) in two healthy adult beagles. Each dog received ALLO (1 mg/kg, IV), and after a washout period of 2 weeks, the dog was dosed with MDZ (0.2 mg/kg, IV) followed 10 min later by ALLO. Behavioral state, vital signs, arterial blood gasses, blood chemistries, and plasma ALLO concentrations were monitored for up to 6 h after dosing.The dogs appeared sleepy but were fully responsive after both treatments. No depression of mean arterial pressure or respiratory rate was noted. Blood gas measurements failed to show evidence of drug-induced acute respiratory acidosis.Estimated maximum plasma ALLO concentrations were in the range of 1500 to 3000 ng/mL. The results indicate that intravenous ALLO can be used safely to treat benzodiazepine-refractory SE, even when administered shortly after a benzodiazepine.

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Tolerability and pharmacokinetics of intravenous allopregnanolone with and without midazolam pretreatment in two healthy dogs

Cited by 2 publications

References 20 publications

ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats

ACVIM Consensus Statement on the management of status epilepticus and cluster seizures in dogs and cats

Tolerability and pharmacokinetics of intravenous allopregnanolone with and without midazolam pretreatment in two healthy dogs

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