Levetiracetam Rectal Administration in Healthy Dogs

Journal of Veterinary Internal Medicine (Impact Factor: 1.88). 01/2014; 28(2). DOI: 10.1111/jvim.12269
Source: PubMed


Levetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in managing SE and CS.
Levetiracetam is rapidly absorbed after rectal administration in dogs and maintains target serum concentrations for at least 9 hours.
Six healthy privately owned dogs between 2 and 6 years of age and weighing 10-20 kg.
Levetiracetam (40 mg/kg) was administered rectally and blood samples were obtained immediately before (time zero) and at 10, 20, 40, 60, 90, 180, 360, and 540 minutes after drug administration. Dogs were observed for signs of adverse effects over a 24-hour period after drug administration.
CLEV at 10 minutes was 15.3 ± 5.5 μg/mL (mean, SD) with concentrations in the target range (5-40 μg/mL) for all dogs throughout the sampling period. Cmax (36.0 ± 10.7 μg/mL) and Tmax (103 ± 31 minutes) values were calculated and 2 disparate groups were appreciated. Dogs with feces in the rectum at the time of drug administration had lower mean Cmax values (26.7 ± 3.4 μg/mL) compared with those without (45.2 ± 4.4 μg/mL). Mild sedation was observed between 60 and 90 minutes without other adverse effects noted.
This study supports the use of rectally administered levetiracetam in future studies of clinical effectiveness in the management of epileptic dogs.

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    ABSTRACT: Levetiracetam is an anticonvulsant used for control of canine epilepsy. An extended release preparation should improve dosing convenience. To determine the disposition of extended release levetiracetam in normal dogs after single dosing. Pharmacokinetic study: 16 healthy, adult dogs. Using a partially randomized crossover study, levetiracetam (30 mg/kg) was administered intravenously (IV) and orally (PO) as extended release preparation with or without food. Blood was collected for 24 hours (IV) or 36 hours (PO). Serum levetiracetam was quantitated by immunoassay and data were subjected to noncompartmental analysis. 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. Extended release levetiracetam (30 mg/kg q12h), with or without food, should maintain concentrations above the recommended minimum human therapeutic concentration. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.
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