Pharmacokinetics of Levetiracetam in Healthy Hispaniolan Amazon Parrots (Amazona ventralis) Following Oral Administration of a Single Dose
American Association of Zoo Veterinarians Conference 2013
Rodney Schnellbacher1, DVM; Hugues Beaufrère2, DrMedVet, DECZM (Avian), DABVP (Avian); Robert D. Arnold3, PhD; Thomas N. Tully, Jr.2, DVM, MS, DABVP (Avian), DECZM (Avian); Joerg Mayer1, DVM, MS, DABVP (ECM), DECZM (Small Mammal); Stephen J. Divers1, BVetMed, DZooMed, DECZM (Herpetology, Zoo Health Management), DACZM, FRCVS
1Department of Small Animal Medicine and Surgery (Zoological Medicine), University of Georgia, Athens, GA, USA; 2Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA; 3Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA

Abstract

Avian long-term anticonvulsive treatments have been poorly described and few pharmacokinetics studies have been performed, with mixed results. Levetiracetam, a new anticonvulsive drug, has shown good efficacy for monotherapy or adjunctive treatment of seizures in both human and veterinary medicine. Pharmacokinetic studies in domestic animals have shown it to have a favorable profile with rapid oral absorption, absence of hepatic metabolism, and a high safety margin.

The aim of this study was to determine the pharmacokinetics of oral levetiracetam in Hispaniolan amazon parrots, Amazona ventralis. Twenty healthy individuals were divided into two treatment groups and were administered either a 50 or a 100 mg/kg dose. Blood samples were collected at baseline and intermittently for 16 hours. No animals showed any adverse behavioral effects to either dosing. Levetiracetam was quantitated in serum using an ARK Diagnostic Levetiracetam® Immunoassay (Sunnyvale, CA) on a Siemens Dimension Xpand (New York, NY) general chemistry analyzer.

Mean pharmacokinetic parameters were estimated using a non-compartmental analysis. The concentration time profiles resembled characteristic absorption, with maximum plasma concentrations (Cmax) of 56.5 and 93.9 mg/L (Tmax) at 30 to 60 min; terminal half-lives (t1/2) at 2.38 and 2.37 hours; volumes of distribution (Vd) at 0.807 and 0.773 L/kg; areas under the curve (AUC) of 14,125 and 28,182 mg•min/L, and clearance rates (Cl) at 3.65 and 3.60 mL/min/kg for 50 mg/kg and 100 mg/kg, respectively. Plasma concentrations were greater than 5 mg/L for up to 9.4 and 12 hours, suggesting an 8-hour and 12-hour oral dosing at 50 and 100 mg/kg, respectively, would be sufficient to maintain systemic drug levels at or above what has been found to be clinically therapeutic in humans.

Acknowledgments

The authors wish to thank the Association of Avian Veterinarians Research Grant, the South Alabama Bird Club, the Gulf South Bird Club, and the Kaytee Avian Foundation for their partial funding of this study as well as the Zoological Medicine Department of Louisiana State University School of Veterinary Medicine and the Zoological Medicine Departments of the University of Georgia Veterinary Teaching Hospital for their support.

Literature Cited

1.  Gidal B.E., E. Baltès, C. Otoul, E. Perucca. 2005. Effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs: a pooled analysis of data from randomized clinical trials. Epilepsy Res. 64:1–11.

2.  Moore S.A., K.R. Muñana, M.G. Papich, J. Nettifee-Osborne. 2010. Levetiracetam pharmacokinetics in healthy dogs following oral administration of single and multiple doses. Am J Vet Res. 71:337–341

3.  Powers L.V., M.G. Papich. 2011. Pharmacokinetics of orally administered phenobarbital in African grey parrots (Psittacus erithacus erithacus). J Vet Pharm Ther. 1365–1368.

 

Speaker Information
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Rodney Schnellbacher, DVM
Department of Small Animal Medicine and Surgery
University of Georgia
Athens, GA, USA


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