Single intravenous and oral dose pharmacokinetics of the antiseizure medication brivaracetam in healthy cats.

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2024-07-17 DOI:10.1111/jvp.13473
Tom Jukier, Chu Zhang, Robert D Arnold, Amanda Gross
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Abstract

The number of available antiseizure medications with demonstrated efficacy in cats is limited. As such, there is a need to evaluate the pharmacokinetics of newer medications so that proper dosing regimens can be made. Brivaracetam (BRV) is a more potent analogue of levetiracetam, and is Food and Drug Administration approved for use in people. The goal of this study was to describe the pharmacokinetics of intravenous and oral doses of BRV in healthy cats. A cross-over study involving eight healthy cats, that were administered 10 mg of BRV intravenously as a bolus and orally in the fasted state. Blood samples were collected over 24 h. Analysis was performed using liquid chromatography-mass spectrometry. Data were subjected to non-compartmental analysis. Median (min-max) of maximal concentration, time to maximal concentration, area under the curve, elimination half-life and oral absolute bioavailability were 902 (682-1036) ng/mL, 0.6 (0.5-2.0) h, 6.4 (5.2-7.2) h, 8145 (6669-9351) ng × h/mL and 100% (85-110) respectively. BRV appeared to be well tolerated by all cats. A single dose of BRV is well tolerated both orally and intravenously. Maximal concentrations are produced rapidly and within the human reference interval considered to be therapeutic.

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在健康猫体内单次静脉注射和口服抗癫痫药物布瓦西坦的药代动力学。
经证实对猫有疗效的抗癫痫药物数量有限。因此,有必要对较新药物的药代动力学进行评估,以便制定适当的用药方案。布里瓦西坦(Brivaracetam,BRV)是左乙拉西坦的一种药效更强的类似物,已被美国食品药品管理局批准用于人类。本研究的目的是描述健康猫静脉注射和口服 BRV 的药代动力学。这项交叉研究涉及 8 只健康猫,分别在空腹状态下静脉注射和口服 10 毫克 BRV。采用液相色谱-质谱法进行分析。对数据进行了非室分析。最大浓度中值(最小-最大)、达到最大浓度的时间、曲线下面积、消除半衰期和口服绝对生物利用度分别为 902(682-1036)纳克/毫升、0.6(0.5-2.0)小时、6.4(5.2-7.2)小时、8145(6669-9351)纳克×小时/毫升和 100%(85-110)。所有猫都能很好地耐受 BRV。口服和静脉注射单剂量 BRV 的耐受性都很好。最大浓度的产生速度很快,且在被认为具有治疗作用的人类参考区间内。
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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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