Disposition of HI-6 oxime in rats after intravenous and intramuscular administration

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Abstract
The pharmacokinetics of HI-6, a cholinesterase-reactivating oxime, were studied in rats, following intravenous or intramuscular administration. A two-compartment model was used to analyse the intravenous data and a one-compartment open model with first-order absorption was used for intramuscular data. Drug concentration had no influence on rate and extent of absorption of intramuscular injections, and bioavailability was 100%. Peak plasma concentrations of HI-6 occurred 15 min after intramuscular injection. No significant differences were found between mean values for half-life, plasma clearance, volume of distribution and area under the plasma concentration versus time curve for the two intramuscular doses and the intravenous dose used. Mean HI-6 plasma concentrations were 140.5 ± 4.2 μg ml−1 3 min after 20 mg ml−1 i.v., with a mean elimination half-life of 65.2 ± 21 min. Plasma clearance rate was 3.95 ± 0.93 ml min−1 kg and the apparent volume of distribution was 0.38 ± 0.17 litre kg−1. The oxime is rapidly distributed in and eliminated by rats when administered intravenously or intramuscularly.

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