Protein-Binding of Cefovecin (Convenia®) in 25 Zoological Species: A Predictor for Extended Duration of Action
Abstract
Cefovecin is a 3rd-generation cephalosporin with an efficacy of two-weeks following a single injection in dogs and cats.9,10 Studies evaluating cefovecin in non-domestic animals are increasing, with pharmacokinetic and elimination studies already completed in various species including six reptile2,11, eight birds2,4,8,11, four primates1,2,7, four ruminants2, three felids2, four marine mammals2-4, sting rays4, rabbits5, and ferrets2,6. The cefovecin half-life is variable (0.9 hour in domestic fowl to greater than four weeks in Patagonian sea lions).1-11 Several theories have been proposed for the prolonged cefovecin elimination rate including extensive renal tubular reabsorption and high plasma protein-binding.9,10,12 Cefovecin is highly protein bound in dogs (96%–98.7%) and cats (>99.5%),9,10 but has not been evaluated in non-domestic species, except for primates. In this study, cefovecin in vitro protein-binding was evaluated in plasma from 25 non-domestic species. Animals of the order Carnivora demonstrated protein-binding levels >99%, which is supportive of the long half-life seen in related species.2-4,6,9,10 Additionally, barasingha deer, okapi, bottlenose dolphins, and red river hogs had protein-binding levels >99%. Elimination studies have demonstrated a long half-life of cefovecin in bottlenose dolphins and domestic swine,2,3 but studies on cervid and giraffid species are lacking. All reptiles, birds, aardvarks, gazelles, and equids showed lower protein-binding (0–94%), which corresponds to the short half-life observed in the literature for related species.2,4 These results suggest that a high degree of protein-binding may be predictive of species in which cefovecin would have an extended duration of action. These findings may also aid in selecting species for cefovecin pharmacokinetic research.
Acknowledgments
The authors would like to thank the Wildlife Conservation Society animal care staff, Wildlife Health Center technical staff, and the staff at the College of Veterinary Medicine Pharmacology Analytical Laboratory, North Carolina State University, the Marine Mammal Center, the U.S. Navy Marine Mammal Program, the National Aquarium, Mr. David Kim, Dr. Craig Harms, Dr. Mads Bertelsen, and Dr. Daniel Garcia-Parraga for their contributions.
This study was reviewed and approved by the Wildlife Conservation Society Institutional Animal Care and Use Committee. Project Number: 09:05
Literature Cited
1. Bakker J, Thuesen LR, Braskamp G, Skaanild MT, Ouwerling B, Langermans JAM, Bertelsen MF. Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta): a pharmacokinetic study. J Vet Pharmacol Ther. 2011. In press. doi: 10.1111/j.1365-2885.2010.01265.x.
2. Bertelsen MF, Thuesen LR, Bakker J, Hebel C, Grøndhal C, Brimer L, Skaanild MT. Limitations and usage of cefovecin in zoological practice. Proc Int Conf Dis Zoo Wild Anim. 2010:140–141.
3. Garcia-Parraga D, Gilabert JA, Valls M, Ros-Rodriguez JM, Alvaro T, Rojo-Solis C, Encinas T. Pharmacokinetics of cefovecin (ConveniaTM) after intramuscular administration to dolphins (Tursiops truncatus) and sea lion (Otaria flavescens). Proc Int Assoc Aquatic Anim Med. 2010:42.
4. Garcia-Parraga D, Rodriguez JM, Alvaro T, Gilabert JA, Valls M, Rojo-Solis C, Garcia-Moratella D, Encinas T. Preliminary study of cefovecin (Convenia©) pharmacokinetics in several aquatic species. Proc Symp Euro Assoc Aquatic Mammals. 2010.
5. Gilabert JA, Ros-Rodriguez JM, Rojo-Solis C, Pérez-Nogués M, Encinas MT. Pharmacokinetics of cefovecin in rabbits. Abstract of the XXXII Congress of the Spanish Society of Pharmacology. Eur J Clin Pharm. 2010;66(1):S55.
6. Montesinos A, Diez-delgado I, Gilbert JA, Ardiaca M, Ros-Rodriguez JM, Encinas T. Pharmacokinetics of cefovecin (Convenia™) by subcutaneous route in ferrets (Mustela putorius furo). Proc Int Conf Dis Zoo and Wild Anim. 2010:231–232.
7. Papp R, Popovic A, Kelly N, Tschirret-Guth R. Pharmacokinetics of cefovecin in squirrel monkey (Saimiri sciureus), rhesus macaques (Macaca mulatta), and cynomologus macaques (Macaca fascicularis). J Am Assoc Lab Anim Sci. 2010;49:805–808.
8. Schink B, Korbel RT. Investigations on pharmacokinetics and pharmacodynamics of cefovecin in domestic pigeons. Proc Assoc Av Vet. 2010:301.
9. Stegemann MR, Sherington J, Blanchflower S. Pharmacokinetics and pharmacodynamics of cefovecin in dogs. J Vet Pharm Therap. 2006;29:501–511.
10. Stegemann MR, Sherington J, Coati N. Pharmacokinetics of cefovecin in cats. J Vet Pharm Therap. 2006;29:513–524.
11. Thuesen LR, Bertelsen MF, Brimer L, Skaanild MT. Selected pharmacokinetic parameters for cefovecin in hens and green iguanas. J Vet Pharm Therap. 2009;32:613–617.
12. Wernick MB, Müntener CR. Cefovecin: a new long-acting cephalosporin. J Exotic Pet Med. 2010;19:317–322.