Disposition of Extended Release Levetiracetam in Normal Healthy Dogs After Single Oral Dosing

BACKGROUND Levetiracetam is an anticonvulsant used for control of canine epilepsy. An extended release preparation should improve dosing convenience. OBJECTIVES To determine the disposition of extended release levetiracetam in normal dogs after single dosing. ANIMALS Pharmacokinetic study: 16 healthy, adult dogs. METHODS Using a partially randomized crossover study, levetiracetam (30 mg/kg) was administered intravenously (i.v.) and orally (p.o.) as extended release preparation with or without food. Blood was collected for 24 hours (i.v.) or 36 hours (p.o.). Serum levetiracetam was quantitated by immunoassay and data were subjected to noncompartmental analysis. RESULTS Pharmacokinetic parameters for fasted versus fed animals, respectively, were (mean ± SEM): Cmax = 26.6 ± 2.38 and 30.7 ± 2.88 μ/mL, Tmax = 204.3 ± 18.9 and 393.8 ± 36.6 minutes, t1/2 = 4.95 ± 0.55 and 4.48 ± 0.48 hours, MRT = 9.8 ± 0.72 and 10 ± 0.64 hours, MAT = 4.7 ± 0.38 and 5.6 ± 0.67 hours, and F = 1.04 ± 0.04 and 1.26 ± 0.07%. Significant differences were limited to Tmax (longer) and F (greater) in fed compared to fasted animals. Serum levetiracetam concentration remained above 5 μ/mL for approximately 20 hours in both fasted and fed animals. CONCLUSIONS AND CLINICAL IMPORTANCE Extended release levetiracetam (30 mg/kg q12h), with or without food, should maintain concentrations above the recommended minimum human therapeutic concentration.