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

Am J Vet Res. 2015 Aug;76(8):719-23. doi: 10.2460/ajvr.76.8.719.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics*
  • Area Under Curve
  • Chromatography, High Pressure Liquid / veterinary
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Dogs / metabolism*
  • Female
  • Levetiracetam
  • Male
  • Piracetam / administration & dosage
  • Piracetam / analogs & derivatives*
  • Piracetam / pharmacokinetics
  • Tablets
  • Tandem Mass Spectrometry

Substances

  • Anticonvulsants
  • Delayed-Action Preparations
  • Tablets
  • Levetiracetam
  • Piracetam