Trainee: Brendan Noonan, Resident in Avian Medicine and Surgery
Co-Principal Investigators: James Morrisey; Curtis Dewey; Dawne Boothe (Auburn University)
Contact Information: Email: firstname.lastname@example.org; Phone: 607-253-4220
Sponsor: Clinical Research Grants Program
Grant Number: N/A
Title: Pharmacokinetics of the Anti-epilepsy Drug Zonisamide in Domestic Chickens
Annual Direct Cost: $6,270
Project Period: 02/01/11-01/31/12
DESCRIPTION (provided by applicant): Birds with epilepsy are commonly presented to veterinarians for evaluation and treatment. Traditional antiepileptic drugs including phenobarbital and potassium bromide appear to be safe to used in birds but not effective, with lack of clinical response, inadequate blood levels and development of sedation with use of higher doses reported by many clinicians. Despite common presentation and use of these medications, there is only a single pharmacokinetic study of phenobarbital in birds. Birds receiving 10 times the dog dose were found to have a very short elimination half life (1.43 hours in comparison with 37-75 hours in dogs) (Papich 2009). These results in the face of high dosages suggest high and fast drug metabolism and support the reported lack of clinical and therapeutic response. Many companion birds with epilepsy face euthanasia as a result of poor response to the available treatment options.
Zonisamide, a sulfonamide derivative antiepileptic drug (AED), has been shown to be both safe and effective when used alone or as adjuvant therapy for treatment of drug resistant epilepsy (Dewey et al 2004; Klopman et al 2007, Shinnar et al, 2008, Wroe et al 2008). According to one study, adding ZNS improved seizure control in 80-90% of dogs with seizures poorly controlled by other drugs (Dewey et al 2004, Orito et al 2008). Zonisamide is also appealing to the veterinary community for its long half life (15h canine serum) and low incidence of side effects. This is especially important in avian medicine considering the higher metabolism of birds and difficulty administering medications several times per day.
During the first phase of the project, we propose to describe the pharmacokinetics of single dose zonisamide in chickens. In the phase 2 of the project, we propose to investigate 4 different doses of ZNS given repeatedly in a dose-escalation matter. This allows us to determine dose dependency, time to achieve steady state and pharmacokinetic parameters for each escalating dose. Based on clinical examination, blood chemistry and post mortem examination we hope to elucidate any adverse drug effects that might be encountered at each elevated dose interval. We will also be able to determine safe and effective oral dosing regimens which maintain blood concentration of the drug within the antiepileptic range recommended for mammals, and to provide recommendations for therapeutic drug monitoring protocols.
The proposed project will take approximately 6-8 weeks. The roles of each investigator are follows:
Principal investigator Dr. Ricardo de Matos; project design, sample collection, examination and assessment of birds during the study, data analysis.
Clinical Trainee Dr. Brendan Noonan DVM: Project design, sample collection, examination and assessment of birds during the study, data analysis.
James Morrisey, DVM, Dipl. ABVP (Avian): Assist with procedures, data collection, examination of birds.
Curtis Dewey, DVM, MS, Dipl. ACVIM (neurology), Dipl. ACVS: Data analysis and interpretation.
Dawn Boothe, DVM, MS, PhD: project design, sample analysis and intepretation.