Department of Molecular Biosciences, University of California, Davis (UC Davis) School of Veterinary Medicine, Davis, California, USA.
Campus Veterinary Services, UC Davis, Office of Research, Davis, California, USA.
Epilepsia Open. 2023 Jun;8(2):666-672. doi: 10.1002/epi4.12723. Epub 2023 Apr 26.
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, each dog was dosed with MDZ (0.2 mg/kg, IV) followed 10 minutes later by ALLO. Behavioral state, vital signs, arterial blood gases, blood chemistries, and plasma ALLO concentrations were monitored for up to 6 hours 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.
神经甾体化合物别孕烯醇酮（ALLO）作为苯二氮䓬类药物难治性癫痫持续状态（SE）的治疗方法正在研究中。在此，我们评估了在两只健康成年比格犬中单独使用和在推荐的咪达唑仑（MDZ）临床剂量后静脉内 ALLO 的心肺安全性。每只狗接受 ALLO（1mg/kg，IV），在 2 周洗脱期后，每只狗接受 MDZ（0.2mg/kg，IV），10 分钟后给予 ALLO。在给药后长达 6 小时监测行为状态、生命体征、动脉血气、血液化学和血浆 ALLO 浓度。两种治疗后，狗都表现出困倦但完全有反应。未观察到平均动脉压或呼吸率下降。血气测量未显示药物引起的急性呼吸性酸中毒的证据。估计的最大血浆 ALLO 浓度在 1500 至 3000ng/ml 范围内。结果表明，静脉内 ALLO 即使在苯二氮䓬类药物给药后不久也可安全用于治疗苯二氮䓬类药物难治性 SE。
