Efficacy and Pharmacokinetic Evaluation of a Dose of Diazepam That Will Reducethe Incidence of Convulsions in Indian Rhesus Monkeys Pretreated with Pyridostigmine Bromide, Challenged with Soman, and Treated with Atropine and Pralidoxime Chloride with the

摘要

A study was initiated to determine the smallest dose of diazepam that wouldresult in no more than a 20 percent incidence of convulsions in male rhesus monkeys pretreated with pyridostigmine, challenged with soman, and post treated with atropine and 2-PAM in conjunction with diazepam. Additionally, the pharmacokinetic parameters for diazepam in monkeys were determined using the effective dose of diazepam determined in the efficacy portion. The estimated 90 min diazepam ED 80 was 112 micrograms/kg and the 4 hr ED 80 was 230 micrograms/kg both with wide confidence limits. The pharmacokinetics were run at 70, 110, and 220 micrograms/kg of diazepam.