• 1. Schwartz-Porsche D, Loscher W, Frey HH. Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. J Vet Pharmacol Ther 1985; 8: 113119.

    • Search Google Scholar
    • Export Citation
  • 2. von Klopmann T, Rambeck B, Tipold A. Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs. J Small Anim Pract 2007; 48: 134138.

    • Search Google Scholar
    • Export Citation
  • 3. Munana KR, Thomas WB, Inzana KD, et al. Evaluation of levetiracetam as adjunctive treatment for refractory canine epilepsy: a randomized, placebo-controlled, crossover trial. J Vet Intern Med 2012; 26: 341348.

    • Search Google Scholar
    • Export Citation
  • 4. Platt SR, Adams V, Garosi LS, et al. Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy. Vet Rec 2006; 159: 881884.

    • Search Google Scholar
    • Export Citation
  • 5. Volk HA, Matiasek LA, Lujan Feliu-Pascual A, et al. The efficacy and tolerability of levetiracetam in pharmacoresistant epileptic dogs. Vet J 2008; 176: 310319.

    • Search Google Scholar
    • Export Citation
  • 6. Patterson EE, Goel V, Cloyd JC, et al. Intramuscular, intravenous and oral levetiracetam in dogs: safety and pharmacokinetics. J Vet Pharmacol Ther 2008; 31: 253258.

    • Search Google Scholar
    • Export Citation
  • 7. Peltola J, Coetzee C, Jimenez F, et al. Once-daily extended-release levetiracetam as adjunctive treatment of partial-onset seizures in patients with epilepsy: a double-blind, randomized, placebo-controlled trial. Epilepsia 2009; 50: 406414.

    • Search Google Scholar
    • Export Citation
  • 8. Wright C, Downing J, Mungall, et al. Clinical pharmacology and pharmacokinetics of levetiracetam. Front Neurol 2013; 44: 192.

  • 9. Kellelheim AS, Stedman MR, Bubrick EJ, et al. Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: a systematic review and meta-analysis. Drugs 2010; 70: 605621.

    • Search Google Scholar
    • Export Citation
  • 10. Bankstahl M, Bankstahl JP, Loscher W. Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy? A pharmacokinetic study with two oral formulations (Luminal vet, Phenoleptil) in dogs. BMC Vet Res 2013; 9: 202.

    • Search Google Scholar
    • Export Citation
  • 11. Moore SA, Munana KR, Papich MG, et al. The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital. J Vet Pharmacol Ther 2010; 34: 3134.

    • Search Google Scholar
    • Export Citation

Advertisement

Pharmacokinetic evaluation of immediate- and extended-release formulations of levetiracetam in dogs

View More View Less
  • 1 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 2 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 3 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 4 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 5 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.
  • | 6 Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849.
  • | 7 Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849.
  • | 8 Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849.

Abstract

OBJECTIVE To compare the pharmacokinetics of various formulations of levetiracetam after oral administration of a single dose to healthy dogs.

ANIMALS 6 neurologically normal mixed-breed dogs.

PROCEDURES A crossover study design was used. Blood samples for serum harvest were collected from each dog before and at various points after oral administration of one 500-mg tablet of each of 2 generic extended-release (ER) formulations, 1 brand-name ER formulation, or 1 brand-name immediate-release (IR) formulation of levetiracetam. Serum samples were analyzed to determine pharmacokinetic properties of each formulation by means of ultra–high-performance liquid chromatography with tandem mass spectrometry.

RESULTS No dogs had clinically important adverse effects for any formulation of levetiracetam. All ER formulations had a significantly lower maximum serum drug concentration and longer time to achieve that concentration than did the IR formulation. Half-lives and elimination rate constants did not differ significantly among formulations. Values for area under the drug concentration-versus-time curve did not differ significantly between ER formulations and the IR formulation; however, 1 generic ER formulation had a significantly lower area under the curve than did other ER formulations.

CONCLUSIONS AND CLINICAL RELEVANCE All ER formulations of levetiracetam had similar pharmacokinetic properties in healthy dogs, with some exceptions. Studies will be needed to evaluate the clinical efficacy of the various formulations; however, findings suggested that twice-daily administration of ER formulations may be efficacious in the treatment of seizures in dogs.

Contributor Notes

Dr. Boozer's present address is Friendship Hospital for Animals, 4105 Brandywine St NW, Washington, DC 20016.

Address correspondence to Dr. Boozer (lbm404@gmail.com).