Neurology Resident North Carolina State University Raleigh, North Carolina, United States
Disclosure(s):
Alejandra Mondino, DVM, PhD: No financial relationships to disclose
Abstract: Background Levetiracetam (LEV) is available in immediate-release (LEV-IR) and extended-release (LEV-XR) formulations. LEV-XR allows q12h administration, but dosing can be limited by tablet size. Veterinarians anecdotally recommend breaking LEV-XR tablets for quicker absorption as treatment for cluster seizures. This study compared the pharmacokinetics of intact, split, and crushed LEV-XR tablets in dogs. Hypothesis: Splitting LEV-XR tablets does not alter absorption, while crushing accelerates it. Animals Seven healthy, young adult research beagles Methods Randomized 3×3 crossover pharmacokinetic study with 7-day washouts. Dogs were administered 500mg LEV-XR orally as intact, split, or crushed tablets. Plasma LEV concentrations were measured over 12 hours by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared using mixed-effects models. Results Compared with intact tablets, crushed tablets resulted in higher peak concentrations (maximum concentration; 61.5 vs 46.0 µg/mL; geometric mean ratio [GMR] 1.34, 95% CI 1.05–1.71) and reduced late-phase exposure (area under the concentration–time curve from 8–12 h; 30.0 vs 49.8 µg·h/mL; GMR 0.60, 95% CI 0.46–0.79), consistent with loss of extended-release properties. Crushed tablets were also associated with a shorter duration above the targeted concentration threshold (10 µg/mL; 8.5 vs 10.9 h; mean difference −2.4 h, 95% CI −3.6 to −1.2). No differences were observed between intact and split tablets. Conclusions and Clinical Importance Extended-release properties are preserved by splitting LEV-XR tablets making this a practical option for dosing smaller dogs. Crushing the tablets compromises the extended-release properties, which may be useful during cluster seizures.
