Background: Seizures represent a common neurological cause for hospitalization in cats. To date, however, choices of anti-seizure drugs for cats are limited due to adverse reactions or to inconvenient dosing schedules. Perampanel, a highly selective, non-competitive antagonist of the AMPA subtype of glutamate receptor, is a recently approved anti-seizure medication in humans with a novel mechanism of action.
Objective: Determine the disposition of a single dose of oral perampanel in healthy cats. Animals: Six healthy cats drawn from a research colony.
Methods: A 0.3mg/kg dose of perampanel was administered orally. Blood samples were collected over 72 hours, and plasma perampanel concentration was quantified using high-pressure liquid chromatography. Data were subjected to non-compartmental analysis.
Results: Median (min-max) of maximal concentration, last concentration, time to maximal concentration, last time point, disappearance half-life, and area under the time concentration curve were 52 (38-106) ng/mL, 20 (18-25) ng/mL 1.5 (1-10) hours), 36 (12-48) hours, 22 (13-268) hours and 2117 (793-8648) ng*h/mL. All but one cat failed to reach concentrations considered to be therapeutic in humans (100-1,000ng/mL). All cats appeared to have tolerated a single dose of perampanel. Conclusions and clinical importance: A single 0.3mg/kg dose of perampanel appears to be safe in cats. The half-life may be sufficiently long to allow a q12h dosing interval. However, a dose adjustment may be necessary to achieve concentrations within the human reference interval.
Learning Objectives:
Identify the need for novel anti-seizure medications for feline patients.
Understand how AMPA glutamate receptors may contribute to generation of seizure activity.
Understand the mechanism and pharmacokinetic profile of a novel anti-seizure medication, perampanel.
