Hemoperfusion and pharmacokinetic studies with methamidophos in the rat

A gas chromatographic method for quantifying methamidophos in plasma was developed and used to study the kinetics of methamidophos in the rat and to evaluate the efficacy of hemoperfusion therapy for treating organophosphate insecticide poisoned individuals. Intravenous administration of methamidophos resulted in a plasma decay curve which corresponded to a one compartment pharmacokinetic model with the following pharmacokinetic parameters: t1/2 = 1.5 hr; Vd = 0.81 L/kg; C1 = 5.8 mL/min/kg; kel = 0.45 hr-1. Hemoperfusion with activated charcoal effectively removed methamidophos from the blood of intoxicated rats, and significantly decreased the body burden of methamidophos; 27% of the administered dose of methamidophos was removed during five hours of perfusion. Despite a rapid reduction in the body burden of the insecticide, rats were not protected against a lethal dose of the insecticide. Because of the rapid and slowly reversible inhibition of acetylcholinesterase by organophosphate insecticides, hemoperfusion alone will not improve the clinical status of organophosphate insecticide poisoned patients.