Bonhage M R, Chilcoat C D, Li Q, Melendez V, Flournoy W S
Department of Veterinary Pathology, Division of Laboratory Animal Medicine, Armed Forces Institute of Pathology, Washington, DC, USA.
J Vet Pharmacol Ther. 2009 Apr;32(2):146-53. doi: 10.1111/j.1365-2885.2008.01013.x.
Currently, there is no viable protection against chemical warfare agents for the working dog. Physostigmine (PHY) and scopolamine (SCO) have been shown to protect dogs against nerve agents with minimal side effects. The goal of this study was to investigate whether reported protective SCO/PHY plasma concentrations of 0.2 and 0.7 ng/mL, respectively, could be reached and maintained with minimal side-effects thereby identifying possible pretreatment regimens. Two continuous regimens of SCO/PHY were administered to beagle dogs. The first regimen consisted of administering transdermal SCO and intraocular PHY, the second consisted of transdermal SCO and rectal PHY. SCO/PHY plasma concentrations for each regimen were determined, individual protective times were calculated and a computerized pharmacokinetic analysis was performed. The results showed transdermal SCO and intraocular PHY routes of delivery achieved sustained protective drug concentrations with minimal side-effects and the rectal route of delivery did not. Group median protective times for the first regimen were 54.45 h for SCO and 64.35 h for PHY, and for the second regimen 63.75 h for SCO and 0 h for PHY. The combined transdermal patch and intraocular regimen may provide a safe and effective regimen against nerve agent poisoning in dogs.
目前,还没有针对工作犬的可行的化学战剂防护措施。毒扁豆碱(PHY)和东莨菪碱(SCO)已被证明能以最小的副作用保护犬类免受神经毒剂侵害。本研究的目的是调查分别报告的0.2和0.7 ng/mL的SCO/PHY血浆浓度是否能在最小副作用的情况下达到并维持,从而确定可能的预处理方案。两种SCO/PHY连续给药方案应用于比格犬。第一种方案包括经皮给予SCO和眼内给予PHY,第二种方案包括经皮给予SCO和直肠给予PHY。测定每种方案的SCO/PHY血浆浓度,计算个体保护时间,并进行计算机药代动力学分析。结果表明,经皮给予SCO和眼内给予PHY的给药途径能以最小的副作用实现持续的保护性药物浓度,而直肠给药途径则不能。第一种方案的组中值保护时间,SCO为54.45小时,PHY为64.35小时;第二种方案中,SCO为63.75小时,PHY为0小时。经皮贴片和眼内联合给药方案可能为犬类神经毒剂中毒提供一种安全有效的方案。