Pharmacokinetics of whole IgG equine antivenom: comparison between normal and envenomed rabbits

Abstract

Pharmacokinetics of antivenoms has been mainly studied in normal animals, whereas very little is known on pharmacokinetics in envenomed animals. The aim of this study was to compare pharmacokinetic parameters of whole IgG equine antivenom in normal rabbits and in rabbits suffering a moderate envenoming by intramuscular injection of the venom of the viperid snake Bothriechis lateralis, which induces drastic microvascular alterations. Anti-Micrurus nigrocinctus antivenom was used, instead of polyvalent (Crotalinae) antivenom, to avoid the formation of toxin–antibody complexes which may alter antivenom pharmacokinetics. It was thus possible to study the effect of vascular alterations, i.e., edema and hemorrhage, induced by the venom on IgG antivenom distribution and elimination. An ELISA was utilized to quantify equine IgG antivenom concentration in rabbit serum. In addition, the amount of IgG antivenom extravasated in injected muscles was also determined. Results indicate that there were no significant differences, between control and envenomed rabbits, in any of the pharmacokinetic parameters investigated, thus suggesting that a moderate envenoming by this viperid species does not alter the pharmacokinetics of IgG antivenom. A significantly higher amount of antivenom IgG was observed in muscle from envenomed rabbits than in muscle from control animals. However, this corresponds to a low percentage of the administered antivenom and, therefore, this increased local extravasation does not have a significant impact in the overall antivenom pharmacokinetics.