Pharmacokinetic Studies of Intramuscular Midazolam in Guinea Pigs Challenged With Soman

摘要

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.