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多次给予健康猫缓释型左乙拉西坦后血清左乙拉西坦浓度及不良事件

Serum levetiracetam concentrations and adverse events after multiple dose extended release levetiracetam administration to healthy cats.

作者信息

Barnes Heller Heidi, Granick Martin, Van Hesteren Mathew, Boothe Dawn M

机构信息

University of Wisconsin-Madison, Madison, Wisconsin.

Auburn University, Auburn, Alabama.

出版信息

J Vet Intern Med. 2018 May;32(3):1145-1148. doi: 10.1111/jvim.15129. Epub 2018 Apr 19.

Abstract

BACKGROUND

Multiple dose administration of antiepileptic drugs to cats presents a challenge for owners. Extended release levetiracetam (XRL) has once daily recommended dosing interval, but multiple dose administration of XRL has not been evaluated in cats.

OBJECTIVE

Evaluate serum levetiracetam concentrations and adverse clinical effects after 11 days of once daily XRL administration to healthy cats.

ANIMALS

Nine healthy privately owned cats, body weight ≥ 5 kg METHODS: Extended release levetiracetam (500 mg/cat) was administered PO q24h for 10 days. On day 11, blood was collected at trough, 4, 6, and 8 hours after tablet administration. Owners maintained records of adverse effects throughout study. Levetiracetam was quantitated in serum using immunoassay validated in cats.

RESULTS

Median dose 94.3 mg/kg q24h. Median (range) trough, 4, 6, and 8 hour serum levetiracetam concentrations were 7.0 (2.3-14.1), 82.6 (7.8-125.3), 92.3 (13.3-97.3), and 72 (22.8-96.4) μg/mL, respectively. Peak was not observed in 4 cats because of missed samples (n = 2) and failure to reach maximal concentration (C ) by 8 hours (n = 2). Median time of maximal concentration (T ) for the remaining 5 cats 5.2 (range 4-6) hours. Adverse effects were minimal and included ataxia (n = 1), sedation (n = 1), and vomiting or regurgitation (n = 1). All signs resolved without dose adjustment or additional treatment.

CONCLUSIONS AND CLINICAL IMPORTANCE

Mean trough serum levetiracetam concentrations were ≥5 μg/mL and adverse effects were minimal throughout dosing period, indicating that the drug was well tolerated. Once daily XRL (500 mg/cat) administration may provide an easier alternative to 3 times daily dosing of intermediate-release levetiracetam for epileptic cats.

摘要

背景

给猫多次服用抗癫痫药物对主人来说是一项挑战。缓释左乙拉西坦(XRL)建议每日给药一次,但尚未在猫身上评估多次服用XRL的情况。

目的

评估对健康猫每日一次给予XRL 11天后的血清左乙拉西坦浓度及不良临床效应。

动物

9只体重≥5 kg的健康家养猫

方法

给予缓释左乙拉西坦(500 mg/猫),口服,每24小时一次,共10天。在第11天,于给药前、给药后4、6和8小时采集血液。在整个研究过程中,主人记录不良反应。使用在猫身上验证过的免疫分析法对血清中的左乙拉西坦进行定量。

结果

中位剂量为94.3 mg/kg,每24小时一次。给药前、给药后4、6和8小时血清左乙拉西坦浓度的中位数(范围)分别为7.0(2.3 - 14.1)、82.6(7.8 - 125.3)、92.3(13.3 - 97.3)和72(22.8 - 96.4)μg/mL。4只猫未观察到峰值,原因是样本遗漏(n = 2)以及在8小时内未达到最大浓度(Cmax)(n = 2)。其余5只猫达到最大浓度(Tmax)的中位时间为5.2(范围4 - 6)小时。不良反应轻微,包括共济失调(n = 1)、镇静(n = 1)以及呕吐或反流(n = 1)。所有症状在未调整剂量或进行额外治疗的情况下均得到缓解。

结论及临床意义

在整个给药期间,血清左乙拉西坦的平均谷浓度≥5 μg/mL,且不良反应轻微,表明该药物耐受性良好。对于患有癫痫的猫,每日一次给予XRL(500 mg/猫)可能比每日三次给予中效释放左乙拉西坦提供一种更简便的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/288c/5980453/671a4935f415/JVIM-32-1145-g001.jpg

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