The Single-Dose Pharmacokinetics of a Compounded Levetiracetam Formulation and Bioequivalence to a Commercial Formulation in Healthy Dogs.

Abstract

Levetiracetam (LEV) is an anti-epileptic drug used extra-label in dogs. Commercially available extended-release formulations (LEV-ER), administered twice daily, cannot be crushed or split, limiting their use in small dogs. A compounded LEV-ER formulation (PO-COMP) can purportedly be partitioned without loss of extended-release properties. The aims of this study were to establish the pharmacokinetic parameters of PO-COMP, divided at the tablet score, and determine the bioequivalence of partitioned PO-COMP to an intact commercially available Food and Drug Administration-approved human oral generic formulation of LEV-ER (PO-COMM). In a randomized crossover design, 12 healthy dogs received a single IV dose (30 mg/kg) of IV-COMM, a single oral dose (500 mg) of intact PO-COMM, or a single oral dose (500 mg) of partitioned PO-COMP and underwent serial measurement of plasma LEV concentrations over 24 h. PO-COMP was bioequivalent to PO-COMM using the 90% confidence interval method for maximum concentration (-3.2% difference [CI -7.4% to -1.1%]) and area under the curve (-14.4% difference [CI -17.8% to 10.8%]). PO-COMP may improve medication adherence and seizure control relative to immediate-release LEV, which requires three times daily dosing. Efficacy studies of PO-COMP are warranted.