In the Literature
Paushter AM, Foss KD, Reinhart JM, Forsythe LE, Hague DW. The single-dose pharmacokinetics of a compounded levetiracetam formulation and bioequivalence to a commercial formulation in healthy dogs. J Vet Pharmacol Ther. 2025;48(2):67-75. doi:10.1111/jvp.13490
The Research …
Levetiracetam is an anticonvulsant drug used alone or in combination therapy for treatment of seizures in dogs. There are no FDA-approved formulations for dogs. Extended-release formulations approved for humans can be administered extra label every 12 hours in dogs.1,2 The smallest available formulation is a 500-mg coated tablet that loses its extended-release properties if the tablet is split, and administration of a full tablet to smaller dogs (<35.3 lb [≈16 kg]) results in a starting dose above the recommended maximum (30 mg/kg).
This 3-way, crossover design studya investigated the pharmacokinetics and bioequivalence of a 500-mg compounded extended-release tablet designed to be split once and maintain its extended-release properties. Dogs (n = 12) enrolled in the study received each of the following treatments in random order, with a 7-day interval between treatments: IV levetiracetam (30 mg/kg), 500-mg commercial extended-release levetiracetam tablet, or 500-mg compounded extended-release levetiracetam tablet split once. Serum samples were collected at predetermined times, and concentrations of levetiracetam were measured using a validated immunoassay. Bioequivalence was determined based on the maximum concentration and area under the curve of the commercial tablets compared with the compounded tablets, with a target confidence interval of −20% to 25%.
Concentrations of levetiracetam were not detectable until up to 4 hours (range, 0.25-4 hours) after administration for either oral formulation. At 12 hours, levetiracetam concentrations were below the minimum therapeutic concentration for humans (5 micrograms/mL) in 2 dogs given the commercial tablet and in 2 dogs given the compounded tablet. The absolute bioavailability (mean ± standard deviation) of the commercial tablet was 95 ± 15% compared with 78 ± 19% for the compounded tablet, although 1 dog had a bioavailability of only 44% with the compounded tablet. The compounded tablet, administered as a split tablet, was bioequivalent to the commercial tablet. As expected, the compounded formulation contained 499.59 mg of levetiracetam per tablet when tested.
… The Takeaways
Key pearls to put into practice:
The results of this study demonstrate oral bioequivalence of this compounded extended-release formulation and the commercial extended-release formulation, despite being split prior to administration, when administered to healthy dogs. The compounded tablet could provide an option for treatment every 12 hours in dogs weighing <35.3 lb (≈16 kg) or that have trouble swallowing larger pills.
Compounded formulations are not tested for safety, strength, or quality and may vary by pharmacy. Other compounded extended-release levetiracetam formulations should not be considered bioequivalent to the formula in this study.
Oral absorption of any extended-release levetiracetam formulation in dogs is variable, and variation is increased with coadministration with other anticonvulsant drugs.3 Additional studies to determine multiple-dose pharmacokinetics, drug-drug interactions, and pharmacodynamic equivalence of this compounded formulation are needed.
The long onset to detection of plasma concentrations precludes use of extended-release formulations in emergency cases.
a Compounded levetiracetam tablets and funding for the IV levetiracetam phase of this study were provided by Epicur Pharma.
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