Despite extensive research for more than six decades on medical countermeasures against
poisoning by
organophosphorus compounds (OP) the treatment options are meagre. The presently established
acetylcholinesterase (AChE) reactivators (
oximes), e.g.
obidoxime and
pralidoxime, are insufficient against a number of
nerve agents and there is ongoing debate on the benefit of
oxime treatment in human OP
pesticide poisoning. Up to now, the therapeutic efficacy of
oximes was mostly evaluated in animal models but substantial species differences prevent direct extrapolation of animal data to humans. Hence, it was considered essential to establish relevant experimental in vitro models for the investigation of
oximes as antidotes and to develop computer models for the simulation of
oxime efficacy in different scenarios of OP
poisoning. Kinetic studies on the various interactions between erythrocyte AChE from various species, structurally different OP and different
oximes provided a basis for the initial assessment of the ability of
oximes to reactivate inhibited AChE. In the present study, in vitro
enzyme-kinetic and pharmacokinetic data from a minipig model of
dimethoate poisoning and
oxime treatment were used to calculate dynamic changes of AChE activities. It could be shown that there is a close agreement between calculated and in vivo AChE activities. Moreover, computer simulations provided insight into the potential and limitations of
oxime treatment. In the end, such data may be a versatile tool for the ongoing discussion of the pros and cons of
oxime treatment in human OP
pesticide poisoning.