Levetiracetam pharmacokinetics in healthy dogs following oral administration of single and multiple doses.

OBJECTIVE

To measure pharmacokinetics of levetiracetam (LEV) after single-dose oral administration in healthy dogs and determine whether pharmacokinetics changed after repeated oral dosing.

ANIMALS

6 healthy adult dogs.

PROCEDURES

Pharmacokinetics were calculated following administration of a single dose (mean, 21.7 mg/kg, PO; day 1) and after administration of the last dose following administration for 6 days (20.8 to 22.7 mg/kg, PO, q 8 h; days 2 to 7). Plasma LEV concentrations were determined by use of high-pressure liquid chromatography. Pharmacokinetic data were analyzed by use of a 1-compartment model with first-order absorption.

RESULTS

Peak concentration occurred 0.6 hours after administration of the first dose, with an absorption half-life of 0.06 hours. Minimal accumulation occurred over the 7 days, with only a slight increase in total area under the concentration-versus-time curve from 268.52 +/- 56.33 h x microg/mL (mean +/- SD) to 289.31 +/- 51.68 h x microg/mL after 7 days. Terminal half-life was 2.87 +/- 0.21 hours after the first dose and 3.59 +/- 0.82 hours after the last dose on day 7. Trough plasma concentrations were variable, depending on the time of day they were measured (morning trough concentration, 18.42 +/- 5.16 microg/mL; midday trough concentration, 12.57 +/- 4.34 microg/mL), suggesting a diurnal variation in drug excretion.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that the pharmacokinetics of LEV did not change appreciably after administration of multiple doses over 7 days. Administration of LEV at a dosage of 20 mg/kg, PO, every 8 hours to healthy dogs yielded plasma drug concentrations consistently within the therapeutic range established for LEV in humans.