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.