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.


OBJECTIVE
To determine the disposition of extended release levetiracetam in normal dogs after single dosing.


METHODS
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
Extended release levetiracetam (30 mg/kg q12h), with or without food, should maintain concentrations above the recommended minimum human therapeutic concentration.
Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
M J
MJ
Beasley
Department of Clinical Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL.
D M
DM
Boothe
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004285:Dogs; D007275:Injections, Intravenous / Q000662:veterinary; D000077287:Levetiracetam; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D000077287:Levetiracetam; D010889:Piracetam
Anticonvulsants; Antiepileptics; Seizures