Pharmacokinetics of single‐dose intravenous levetiracetam administration in normal dogs

Abstract

Abstract Objective: To determine plasma pharmacokinetics of levetiracetam after a single intravenous dose (60 mg/kg) in normal dogs using a high‐performance liquid chromatography assay validated for canine plasma. Design: Pharmacokinetic study. Setting: A university‐based canine research facility. Animals: Six healthy adult dogs. Interventions: Intravenous drug administration, multiple blood sample procurement. Measurements and main results: There were no obvious adverse effects associated with the intravenous (IV) bolus administration of levetiracetam in any of the dogs. Plasma levetiracetam concentrations remained above or within the reported therapeutic range for humans (5–45 μg/mL) for all dogs, for all time periods evaluated. Mean and median (in parentheses) values for pharmacokinetic parameters included the following: maximum plasma concentration, 254 μg/mL (254 μg/mL); half‐life, 4.0 hours (4.0 hours); volume of distribution at steady state, 0.48 L/kg (0.48 L/kg); clearance, 1.4 mL/kg/min (1.5 mL/kg/min); and median residence time, 6.0 hours (6.0 hours). Conclusions: In normal dogs, a 60 mg/kg IV bolus dose of levetiracetam is well tolerated and achieves plasma drug concentrations within or above the therapeutic range reported for humans for at least 8 hours after administration. Based on the favorable pharmacokinetics and tolerability demonstrated for IV levetiracetam in this study, in addition to previously demonstrated efficacy of oral levetiracetam, IV levetiracetam may be a useful treatment option for emergency management of canine seizure activity.