Objective: To describe the pharmacokinetics of the IV formulation of levetiracetam administered intranasally and calculate the absolute bioavailability. Our hypothesis was that levetiracetam would show near complete absorption following a single intranasal dose.
Methods: 8 healthy dogs (4 female, 4 male) from a canine colony were used in a crossover study comparing the pharmacokinetics of intranasal and IV levetiracetam. The study occurred from August through September 2024. A 100-mg dose of levetiracetam was administered via the intranasal and IV routes on separate occasions. Blood was collected from jugular catheters over a 24-hour period following dose administration. Plasma levetiracetam concentrations were analyzed using high-pressure liquid chromatography. Noncompartmental analysis was performed to describe the pharmacokinetics.
Results: Median (minimum to maximum), maximal concentration, time to maximal concentration, and elimination half-life for the intranasal route were 7.85 µg/mL (range, 3.37 to 14.16), 0.98 hours (range, 0.22 to 1.00), and 2.83 hours (range, 2.44 to 3.76), respectively. Median (minimum to maximum) bioavailability was 61% (range, 34% to 85%). The maximal concentration achieved fell within the human reference interval for levetiracetam in 5 of 8 dogs.
Conclusions: Levetiracetam was absorbed to a moderate degree following the intranasal route of administration and appeared to be well tolerated.
Clinical relevance: Levetiracetam is absorbed via the nasal administration route and could be considered a feasible route of administration for at-home rescue protocols. Although concentrations within the human reference interval were achieved in a majority of dogs, a clinical trial is necessary to determine if this method of administration would be effective in a clinical setting.
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