Abstract: Background – Cluster seizures and status epilepticus in dogs are emergencies requiring rapid treatment. Intranasally delivered benzodiazepines have been shown to be effective for early seizure cessation. The pharmacokinetics of longer-acting antiseizure drugs administered intranasally in dogs have not been previously investigated. Hypothesis/Objectives – To describe the single-dose pharmacokinetics of levetiracetam administered intranasally (IN) to healthy dogs compared to intravenous (IV) administration. The investigators hypothesized that IN levetiracetam has pharmacokinetic properties similar to IV administration.Animals – Nine healthy dogsMethods – Dogs were prospectively enrolled in a randomized crossover study to receive a single 30 mg/kg dose of intravenous (100 mg/mL solution, commercial formulation) or intranasal (460 mg/mL solution, compounded formulation) levetiracetam. Serial serum samples were collected over 24 hours. Following a 7-day washout period, this was repeated using the other formulation. Serum concentrations were quantified using LC-MS. Pharmacokinetic analyses were performed using non-compartmental methods. Comparisons between the formulations were made using a Wilcoxon signed-rank test.Results – Cmax was 14.6 ± 5.4 µg/mL with a Tmax of 2.3 ± 1.5 hours. The time to achieve therapeutic concentration (5 µg/mL) for IN was 0.34 ± 0.22 hours (IV 0.25 hours; p = 0.250) and remained above this threshold for 6.57 ± 3.17 hours (IV 9.77 ± 2.11 hours; p = 0.047). The bioavailability for IN administration was 70 ± 27.4%. Conclusions and Clinical Importance – Levetiracetam reaches therapeutic concentrations rapidly when delivered intranasally and may be viable for emergent treatment of seizures when IV access is not available.
