In the field of
antivenom research, development, and manufacture, it is often advised to follow the World Health Organization's (WHO) guidelines for the production, control, and regulation of snake
antivenom immunoglobulins, which recommend the use of preincubation assays to assess the efficacy of
snakebite therapeutics. In these assays,
venom and
antivenom are mixed and incubated prior to in vivo administration to rodents, which allows for a standardizable comparison of
antivenoms with similar characteristics. However, these assays are not necessarily sufficient for
therapeutics with significantly different pharmacological properties than antibody-based
antivenoms, such as small molecule inhibitors, nanoparticles, and other modalities. To ensure that the in vivo therapeutic utility of completely novel toxin-neutralizing molecules with no history of use in envenoming
therapy and variable pharmacokinetics is properly evaluated, such molecules must also be tested in preclinical rescue assays, where rodents are first challenged with appropriate doses of
venoms or toxins, followed by the administration of neutralizing modalities after an appropriate time delay to better mimic the real-life scenarios faced by human
snakebite victims. Such an approach takes the
venom (or toxin) toxicokinetics, the
drug pharmacokinetics, and the
drug pharmacodynamics into consideration. If new modalities are only assessed in preincubation assays and not subjected to evaluation in rescue assays, the publication of neutralization data may unintentionally misrepresent the actual therapeutic efficacy and suitability of the modality being tested, and thus potentially misguide strategic decision making in the research and development of novel
therapies for
snakebite envenoming.