title: Evaluation of two scopolamine and physostigmine pretreatment regimens against nerve agent poisoning in the dog.
abstract: 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.
authors.affiliation: Department of Veterinary Pathology, Division of Laboratory Animal Medicine, Armed Forces Institute of Pathology, Washington, DC, USA. michael.bonhage@osd.afip.mil
authors.forename: M R
authors.initials: MR
authors.lastname: Bonhage
authors.forename: C D
authors.initials: CD
authors.lastname: Chilcoat
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: V
authors.initials: V
authors.lastname: Melendez
authors.forename: W S
authors.initials: WS
authors.lastname: Flournoy
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002618:Chemical Warfare; D018680:Cholinergic Antagonists / Q000493:pharmacokinetics*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004285:Dogs / Q000097:blood* / Q000378:metabolism; D005260:Female; D013058:Mass Spectrometry / Q000662:veterinary; D010830:Physostigmine / Q000097:blood / Q000493:pharmacokinetics*; D011041:Poisoning / Q000188:drug therapy / Q000662:veterinary; D012601:Scopolamine / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D012601:Scopolamine