Pharmacokinetic Studies of Intramuscular Midazolam in Guinea Pigs Challenged With Soman
Abstract
Studies have demonstrated that benzodiazepine compounds are effective at antagonizing seizure activity produced by the organophosphate (OP) cholinesterase inhibitor soman. In this present study we have investigated the pharmacokinetics of midazolam and its associated effects on electroencephalographic (EEG) activity following intramuscular (im) injection to soman-exposed guinea pigs (Crl:(HA)BR). Prior to experiments, the animals were surgically implanted with EEG leads to monitor seizure activity. For the study, animals were administered the following pretreatment/OP/treatment regimen. Pyridostigmine bromide (0.026 mg/kg, im) was given 30 min prior to soman (56 mug/kg,, 2 x LD50; subcutaneously, sc), followed in one minute by atropine sulfate (2 mg/kg, im) and pralidoxime chloride (25 mg/kg, im). All animals receiving this regimen developed seizure activity. Midazolam 0.8 mg/kg, im, was administered 5 min after onset of seizure activity. Based on EEG data, animals were categorized as either seizure-terminated or seizure not-terminated at 30 min following anticonvulsant administration.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA442567
Entities
People
- Benedict R. Capacio
- C. E. Byers
- John H. McDonough
- Joseph P. Smith
- K. A. Merk
Organizations
- United States Army Medical Research Institute of Chemical Defense