Role of the animal model on the pharmacokinetics of equine-derived antivenoms Alicia Rojas a , Mariángela Vargas a , Nils Ramírez b , Ricardo Estrada a , Álvaro Segura a , María Herrera a , Mauren Villalta a , Aarón Gómez a , José María Gutiérrez a , Guillermo León a, * a Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica b Instituto de Investigaciones Farmacéuticas, Facultad de Farmacia, Universidad de Costa Rica, San José, Costa Rica article info Article history: Received 17 August 2012 Received in revised form 6 March 2013 Accepted 22 March 2013 Available online 1 April 2013 Keywords: Venom Equine immunoglobulins Antivenom Pharmacokinetics Heterology abstract Antivenom pharmacokinetics has been studied in heterologous models in which the an- imal species used as immunoglobulin source is different from that used as recipient. In these models, after intravenous administration of antivenom, the plasma concentration of immunoglobulins shows a rapid initial declining-phase followed by a slower terminal- phase, which has been associated with antivenom distribution and elimination, respec- tively. We have compared pharmacokinetic parameters for equine-derived antivenom in homologous (horse) and heterologous (cow) models. It was found that the maximum concentration is lower in cows than in horses. Additionally, the steady-state distribution volume is higher in cows as compared to horses. On the other hand, models were not different in the time required to reach the maximum concentration, the area under the concentration/time curve, the half-life of decay during the slowest phase, the systemic clearance and the mean residence time. Similar results were obtained in a rabbit model, in which the pharmacokinetics was also affected by passive immunization of rabbits with anti-equine IgG. We conclude that, in addition to other physiological differences (e.g. cardiac frequency, plasmatic volume, glomerular filtration rate, etc.) between animal models, the ability to remove foreign immunoglobulins might influence the way in which the plasma concentration of antivenom decreases over time, thereby distorting the pharmacokinetic predictions based on non-compartmental models. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Venoms are mixtures of toxic proteins developed by some animals for prey capture and defense against preda- tors (Wigger et al., 2002; Aird, 2002; Nisani and Hayes, 2011). Each venom component has physicochemical char- acteristics that determine their ability to access different body compartments (Ismail et al., 1998; El Hafny et al., 2002) and to exert toxicity in specific tissue targets. The complex set of local and systemic alterations induced by venom components characterize envenomations by poisonous animals (Pinto et al., 2010; Khattabi et al., 2011; Otero-Patiño et al., 2012). Antivenoms are formulations of immunoglobulins or immunoglobulin fragments, purified from plasma of ani- mals immunized with venoms (Gutiérrez et al., 2011). Currently, antivenom administration is the recommended medical practice to treat envenomations caused by animals such as snakes (WHO, 2010), scorpions (Bahloul et al., 2013), spiders (Offerman et al., 2011; Pauli et al., 2006) and cater- pillars (Caovilla and Guardão, 2004), among others. From a clinical point of view, the success of antivenom * Corresponding author. Tel.: þ506 2511 7888; fax: þ506 2292 0485. E-mail address: guillermo.leon@ucr.ac.cr (G. León). Contents lists available at SciVerse ScienceDirect Toxicon journal homepage: www.elsevier.com/locate/toxicon 0041-0101/$ – see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.toxicon.2013.03.013 Toxicon 70 (2013) 9–14