Single-dose pharmacokinetics of intranasal levetiracetam in healthy dogs

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 antiepileptic drugs administered intranasally in dogs have not been previously investigated. The objectives of this study were to describe the single-dose pharmacokinetics of levetiracetam administered intranasally (IN) in healthy dogs compared to intravenous (IV) administration. We hypothesized that the administration of levetiracetam intranasally would rapidly achieve therapeutic serum concentrations and would remain above the therapeutic cut off for an extended period of time. Nine healthy dogs were prospectively enrolled in a randomized crossover study and assigned 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. Peak concentration (Cmax) following IN administration of levetiracetam 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 and remained above this threshold for 6.57 ± 3.17 hours (compared to IV 9.77 ± 2.11 hours; p = 0.047). The bioavailability for IN administration was 70 ± 27.4%. This study demonstrates that levetiracetam reaches therapeutic concentrations rapidly when delivered intranasally and may be a viable route for emergent treatment of seizures when IV access is not available.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

VMS - Veterinary Clinical Medicine

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2024

Author dc:creator

• Wagner, Jessica L.

Contributors dc:contributor

• Foss, Kari
• Reinhart, Jennifer
• Forsythe, Lauren

• Epilepsy
• Veterinary Medicine
• Neurology
• Seizure Management

Statement dc:rights

• Copyright 2024 Jessica Wagner

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/127216

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F127216