THE STOICHIOMETRY OF PROTECTION AGAINST SOMAN AND VX TOXICITY IN MONKEYS PRETREATED WITH HUMAN BUTYRYLCHOLINESTERASE

Bioscavengers of organophophates (OF) have been examined as potential substitutes for the currently approved drug treatment against OP toxic ity. The present work was designed to assess the ability of butyrylcho linesterase, purified from human serum (HuBChE), to prevent the toxici ty induced by soman and VX in rhesus monkeys. The consistency of the d ata across species was then evaluated as the basis for the extrapolati on of the data to humans. The average mean residence time of the enzym e in the circulation of monkeys following an intravenous loading was 3 4 hr. High bioavailability of HuBChE in blood (>80%) was demonstrated after intramuscular injection. A molar ratio of HuBChE:OP similar to 1 .2 protected against an iv bolus injection of 2.1 x LD50 VX, while a r atio of 0.62 was sufficient to protect monkeys against an iv dose of 3 .3 x LD50 of soman, with no additional postexposure therapy. A remarka ble protection was also seen against soman-induced behavioral deficits detected in the performance of a spatial discrimination task. The con sistency of the results across several species offers a reliable predi ction of both the stoichiometry of the scavenging and the extent of pr ophylaxis with HuBChE against nerve agent toxicity in humans. (C) 1997 Academic Press.