The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital

Levetiracetam (LEV) is a commonly used add-on medication in dogs with refractory epilepsy. The objective of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7-27.8 mg/kg). Blood samples were collected at baseline and intermittently for 24 h. The study was repeated after the dogs received oral PB (2.0-3.3 mg/kg) twice daily for 21 days. Plasma LEV levels were evaluated by high pressure liquid chromatography, and data analyzed using a compartmental model. Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (C-max) from 32.39 +/- 6.76 to 18.22 +/- 8.97 (P = 0.0071), a decrease in elimination half-life (T-1/2) from 3.43 +/- 0.47 to 1.73 +/- 0.22 (P = 0.0005), and an increase in oral clearance from 124.93 +/- 26.93 to 252.99 +/- 135.43 ml/h/kg (P < 0.0001). Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB.