The Pharmacokinetics of Levetiracetam in Healthy Dogs Following Single and Multiple Oral Doses
The use of levetiracetam (LEV) in veterinary medicine is increasing for both refractory and newly diagnosed epileptic patients. Although the pharmacokinetics after a single dose in dogs has been reported, the pharmacokinetics after multiple doses is unknown. The objective of this study was to measure the pharmacokinetics of LEV after an oral dose in dogs, and to determine if the pharmacokinetics would change after repeated dosing. Six healthy dogs were administered a single oral dose of LEV (20.8-22.7mg/kg). Blood samples were collected at baseline and intermittently for 24 hours after a single oral dose, and again after 6 days of Q8h dosing. Plasma LEV concentrations were measured by HPLC. Pharmacokinetic data was analyzed using a compartmental model. Peak (CMAX) concentration occurred in 0.8 hours (TMAX) with absorption T½ of 12 min after the first dose. Minimal accumulation occurred over 6 days. After multiple doses, the CMAX was 61.42 ug/ml ± 11.48, compared with 55.19 µg/mL ± 11.72 after the first dose. The elimination T1/2 was 3.58 h ± 0.79 and absorption T1/2 was 0.19 h ± 0.17. Plasma trough levels were variable depending on the time of day they were collected (18.42 ± 5.16 morning trough vs 12.57 ± 4.34 mid-day trough) suggesting a nocturnal difference in excretion. After multiple doses, the pharmacokinetics did not change appreciably, indicating that multiple doses of LEV does not alter its own pharmacokinetics. Administration of LEV at 20mg/kg orally Q8h produced plasma drug concentrations consistently within the therapeutic range established for LEV in human medicine.