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Pharmacokinetics of intranasal levetiracetam in healthy dogs: a feasible route of administration.

Ewa Krolak,Kamoltip Thungrat,Amanda Gross,K. Gerken,Kendon W. Kuo,T. Jukier

Published 2025 in American Journal of Veterinary Research

ABSTRACT

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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