HI-6 and 2-PAM in sheep: pharmacokinetics and effects on muscle tissue following intramuscular injection

The pharmacokinetics of 2-PAM, a component of the current nerve agent antidote therapy for U.S. military forces was compared to the pharmacokinetics of another acetylcholinesterase reactivator HI-6. Additionally, the effects of these compounds on muscle tissue following intramuscular injection was examined. Plasma concentrations of the oximes were determined by HPLC. Plasma concentration-time profiles for both oximes fit a one-compartment open model with first-order absorption and elimination. The results demonstrate that the half-time of absorption of HI-6 was significantly higher than that for 2-PAM. Musculoirritancy was assessed on the basis of quantitative histological examinations of the injection sites and by the measurement of serum creatinine phosphokinase. Comparison of the scores from the histological sections demonstrate no difference between the two oximes. Serum creatinine phosphokinase values were elevated following injections of HI-6, but were not consistently elevated following the 2-PAM injections.