Pharmacokinetics of levetiracetam after oral and intravenous administration of a single dose to clinically normal cats.

OBJECTIVE

To determine whether therapeutic concentrations of levetiracetam can be achieved in cats and to establish reasonable i.v. and oral dosing intervals that would not be associated with adverse effects in cats.

ANIMALS

10 healthy purpose-bred cats.

PROCEDURES

In a randomized crossover study, levetiracetam (20 mg/kg) was administered orally and i.v. to each cat. Blood samples were collected 0, 10, 20, and 40 minutes and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after administration. Plasma levetiracetam concentrations were determined via high-performance liquid chromatography.

RESULTS

Mean ± SD peak concentration was 25.54 ± 7.97 μg/mL. The mean y-intercept for i.v. administration was 37.52 ± 6.79 μg/mL. Half-life (harmonic mean ± pseudo-SD) was 2.95 ± 0.95 hours and 2.86 ± 0.65 hours for oral and i.v. administration, respectively. Mean volume of distribution at steady state was 0.52 ± 0.09 L/kg, and mean clearance was 2.0 ± 0.60 mL/kg/min. Mean oral bioavailability was 102 ± 39%. Plasma drug concentrations were maintained in the therapeutic range reported for humans (5 to 45 μg/mL) for at least 9 hours after administration in 7 of 10 cats. Only mild, transient hypersalivation was evident in some cats after oral administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Levetiracetam (20 mg/kg) administered orally or i.v. to cats every 8 hours should achieve and maintain concentrations within the therapeutic range for humans. Levetiracetam administration has favorable pharmacokinetics for clinical use, was apparently tolerated well, and may be a reasonable alternative antiepileptic drug in cats.