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

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY
Aaron M Paushter, Kari D Foss, Jennifer M Reinhart, Lauren E Forsythe, Devon W Hague
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引用次数: 0

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.

健康犬体内左乙拉西坦复方制剂的单剂量药代动力学以及与商用制剂的生物等效性。
左乙拉西坦(LEV)是一种抗癫痫药物,可在狗的标签外使用。市售的缓释制剂(LEV-ER)每天给药两次,但不能压碎或分割,限制了其在小型犬中的使用。据称,LEV-ER 复方制剂(PO-COMP)可以分装而不会丧失缓释特性。本研究的目的是确定PO-COMP的药代动力学参数(按片剂分装),并确定分装后的PO-COMP与完整的市售食品药品管理局批准的LEV-ER口服普通制剂(PO-COMM)的生物等效性。在随机交叉设计中,12只健康狗分别接受了单次静脉注射剂量(30毫克/千克)的IV-COMM、单次口服剂量(500毫克)的完整PO-COMM或单次口服剂量(500毫克)的分装PO-COMM,并在24小时内连续测量血浆LEV浓度。采用90%置信区间法计算最大浓度(-3.2%差异[CI -7.4%至-1.1%])和曲线下面积(-14.4%差异[CI -17.8%至10.8%]),PO-COMP与PO-COMM具有生物等效性。与需要每日服药三次的速释 LEV 相比,PO-COMP 可改善服药依从性和癫痫发作控制。有必要对 PO-COMP 进行疗效研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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