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

Abstract

To compare the pharmacokinetics of various formulations of levetiracetam after oral administration of a single dose to healthy dogs. 6 neurologically normal mixed-breed dogs. 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. 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. 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.