Toxicon 48 (2006) 255–263 Pharmacokinetics of whole IgG equine antivenom: Comparison between normal and envenomed rabbits Lil Quesada a , Carlos Sevcik b , Bruno Lomonte a , Ermila Rojas a , Jose´ Marı´a Gutie´ rrez a,Ã a Facultad de Microbiologı´a, Instituto Clodomiro Picado, Universidad de Costa Rica, San Jose´, Costa Rica b Instituto Venezolano de Investigaciones Cientı´ficas, Centro de Biofı´sica y Bioquı´mica, Caracas, Venezuela Received 8 February 2006; received in revised form 29 May 2006; accepted 31 May 2006 Available online 14 June 2006 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. r 2006 Elsevier Ltd. All rights reserved. Keywords: Antivenom; IgG; Envenoming; Pharmacokinetics 1. Introduction Parenteral administration of equine- or ovine- derived antivenoms is the central therapeutic inter- vention in envenomings caused by snakebites (Lalloo and Theakston, 2003). Laboratories produ- cing antivenoms around the globe currently manu- facture three main types of antivenoms, depending on the nature of the active principle of these immunobiologicals. Most antivenoms are made of F(ab 0 ) 2 antibody fragments, obtained by pepsin digestion of whole IgG molecules. Other products consist of whole IgG molecules purified by either ammonium sulfate or caprylic acid precipitation, ARTICLE IN PRESS www.elsevier.com/locate/toxicon 0041-0101/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.toxicon.2006.05.010 Ã Corresponding author. Tel.: +506 2293135; fax: +506 2920485. E-mail address: jgutierr@icp.ucr.ac.cr (J.M. Gutie´rrez).