Single-Dose Pharmacokinetics of Intranasal Levetiracetam in Healthy Dogs

Cluster seizures and status epilepticus in dogs are emergencies requiring rapid intervention. Intranasal (IN) benzodiazepines are effective for early seizure cessation, but the pharmacokinetics of longer-acting antiseizure medications administered IN have not been investigated in dogs. This study aimed to describe the single-dose pharmacokinetics of a compounded IN levetiracetam product (IN-LEV) in healthy dogs. We hypothesized that the administration of IN-LEV to healthy dogs will demonstrate similar pharmacokinetic parameters to IV administration. In a randomized crossover design, nine healthy dogs received a single 30 mg/kg IV dose (100 mg/mL) or a single 30 mg/kg IN dose (460 mg/mL) of levetiracetam. Serum levetiracetam concentrations were serially measured over 24 h. Pharmacokinetic analysis was performed using non-compartmental methods and comparisons between routes of administration were made using the Wilcoxon signed-rank test. C_max, T_max, and t_1/2 for IN-LEV were 14.6 ± 5.4 μg/mL, 2.3 ± 1.5 h, and 3.6 ± 0.4 h, respectively. IN-LEV achieved minimum target concentrations (5 μg/mL) within 0.34 ± 0.22 h and maintained these levels for 6.57 ± 3.17 h. Bioavailability for IN-LEV was 70% ± 27.4%. This study demonstrates that IN levetiracetam rapidly achieves the lowest reference interval concentration, but the high end of the interval was not achieved in any dog with a single 30 mg/kg dose. IN-LEV may be a viable alternative for emergent seizure management when IV access is unavailable, but multiple doses may be required to achieve seizure cessation in some patients.