生长商品猪(Sus scrofa domestica)口服氯硝西泮的药代动力学。

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2024-05-05 DOI:10.1111/jvp.13451
Chiara E. Hampton, Stephanie A. Kleine, Joe S. Smith, Pierre-Yves Mulon, Christopher K. Smith, Gregory A. Shanks, Lucille Ruth Vanecek, Reza Seddighi, Sherry Cox
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引用次数: 0

摘要

氯硝西泮会导致人镇静和精神运动障碍。由于人和猪对苯二氮卓类药物的反应相似,氯硝西泮可能是对猪产生轻度至中度镇静作用的一种可行选择。本研究旨在确定 8 头健康生长的商品杂交猪单次口服氯硝西泮剂量(0.5 毫克/千克)的药动学特征。研究人员在基线和用药后 96 小时内连续采集血浆样本。使用反相高效液相色谱法对血浆浓度进行了量化,并根据时间-浓度数据拟合了区室模型。单室一阶模型最符合数据。最大血浆浓度为 99.5 纳克/毫升,达到最大浓度的时间为 3.4 小时。消除半衰期为 7.3 小时,平均停留时间为 7.4 小时,表观分布容积为 5.7 升/千克。虽然尚未在猪体内研究药效学效应,但所达到的血浆浓度超过了与人的精神运动障碍有关的浓度。猪每 8 小时口服 0.35 毫克/千克的模拟口服方案可使血浆浓度超过 32 纳克/毫升,而这在人体内会产生精神运动障碍。有必要开展进一步研究,测试这些剂量在商品猪和微型猪中的临床疗效。
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Pharmacokinetics of oral clonazepam in growing commercial pigs (Sus scrofa domestica)

Clonazepam causes sedation and psychomotor impairment in people. Due to similarities between people and swine in response to benzodiazepines, clonazepam may represent a viable option to produce mild-to-moderate tranquillization in pigs. The objective of this study was to determine the pharmacokinetic profile of a single oral dose (0.5 mg/kg) of clonazepam in eight healthy, growing commercial cross pigs. Serial plasma samples were collected at baseline and up to 96 h after administration. Plasma concentrations were quantified using reverse-phase high-performance liquid chromatography, and compartment models were fit to time–concentration data. A one-compartment first-order model best fits the data. Maximum plasma concentration was 99.5 ng/mL, and time to maximum concentration was 3.4 h. Elimination half-life was 7.3 h, mean residence time 7.4 h, and apparent volume of distribution 5.7 L/kg. Achieved plasma concentrations exceeded those associated with psychomotor impairment in people although pharmacodynamic effects have not been investigated in pigs. A simulated oral regimen consisting of 0.35 mg/kg administered every 8 h to pigs would achieve plasma concentrations above 32 ng/mL which are shown to produce psychomotor impairment in people. Further studies to test the clinical efficacy of these dosages in commercial and miniature pigs are warranted.

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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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