Correlation of 2-PAM plasma levels after organophosphate intoxication

In order to investigate the pathophysiological effects of organophosphorus poisoning on therapeutic compounds, multiples of the LD50 for sarin and soman were injected into guinea pigs after which 2-PAM and atropine sulfate were administered intramuscularly. It was found that intoxication by sarin or soman in therapeutically treated animals resulted in modifications of plasma oxime concentrations. Peak plasma (CPmax) concentrations and areas under the curve (AUC) between 1 to 10 min after the injection of 2-PAM were altered in a systematic fashion which correlated to the multiple of the LD50 (r greater than 0.9498). The effect of the sarin and soman was studied at fractions of the LD50, i.e. 0.7s, 1.5, 2.2, 2.8, 5.6, 11.2. The influence of the organophosphorus poisons on the plasma concentration of 2-PAM is biphasic. Multiples of the LD50 equal to or below 2.2 tend to decrease, whereas multiples equal to or above 2.8 tend to increase CPmax and AUC in different groups of animals. Changes in the plasma concentrations of 2-PAM may result from alterations in blood flow rates and patterns which would alter the distribution and elimination of 2-PAM.