Mondino Alejandra, Nettifee Julie A, Papich Mark G, Muñana Karen R
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
J Vet Pharmacol Ther. 2025 May 12;48(4):340-3. doi: 10.1111/jvp.13517.
Levetiracetam (LEV) is a commonly used antiseizure medication in dogs, available in immediate-release (LEV-IR) and extended-release (LEV-XR) formulations. LEV-XR improves owner compliance with less frequent dosing, but its lowest concentration tablet (500 mg) often exceeds recommended doses for small dogs. This study evaluated how modifying LEV-XR tablets affects dissolution rates, comparing intact, split, and crushed LEV-XR tablets with intact LEV-IR tablets. Dissolution testing followed United States Pharmacopeia (USP) guidelines for LEV-XR tablets. Tablets were placed in a buffer solution (pH 6.0) and agitated at 100 rpm. Samples were collected at 0, 0.5, 2, 4, 6, and 8 h, then analyzed by high-pressure liquid chromatography (HPLC) using a USP reference standard. Results indicated that splitting LEV-XR tablets slightly increased drug release compared to intact tablets, while crushing eliminated extended-release properties, mimicking LEV-IR dissolution. These findings suggest that splitting LEV-XR tablets may be a viable strategy for dosing small dogs without compromising sustained release. Conversely, crushing LEV-XR tablets may be useful for rapid drug release in cluster seizure protocols. Future pharmacokinetic studies are needed to confirm if these in vitro results correlate with in vivo performance for both maintenance and emergency seizure management in dogs.
左乙拉西坦（LEV）是犬类常用的抗癫痫药物，有速释（LEV-IR）和缓释（LEV-XR）两种剂型。LEV-XR通过减少给药频率提高了主人的依从性，但其最低浓度片剂（500毫克）对小型犬来说往往超过推荐剂量。本研究评估了改变LEV-XR片剂对溶出速率的影响，将完整、掰开和碾碎的LEV-XR片剂与完整的LEV-IR片剂进行比较。溶出度测试遵循美国药典（USP）对LEV-XR片剂的指导原则。将片剂置于缓冲溶液（pH 6.0）中，以100转/分钟的速度搅拌。在0、0.5、2、4、6和8小时收集样品，然后使用USP参考标准通过高压液相色谱（HPLC）进行分析。结果表明，与完整片剂相比，掰开LEV-XR片剂会使药物释放略有增加，而碾碎则消除了缓释特性，类似于LEV-IR的溶出情况。这些发现表明，掰开LEV-XR片剂可能是一种可行的给药策略，既能给小型犬给药，又不会影响其缓释效果。相反，碾碎LEV-XR片剂可能有助于在丛集性癫痫发作方案中实现快速药物释放。未来需要进行药代动力学研究，以确认这些体外结果是否与犬类维持和紧急癫痫发作管理的体内表现相关。
