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健康成年马注射杜拉霉素(延胡索酸泰妙菌素)后的药代动力学和肺部分布。

Pharmacokinetics and pulmonary distribution of Draxxin (tulathromycin) in healthy adult horses.

机构信息

Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA.

Marion duPont Scott Equine Medical Center, Virginia-Maryland College of Veterinary Medicine, Leesburg, VA, USA.

出版信息

J Vet Pharmacol Ther. 2021 Sep;44(5):714-723. doi: 10.1111/jvp.12968. Epub 2021 Mar 14.

Abstract

The objective of this study was to determine the pharmacokinetics and tolerability of tulathromycin (Draxxin ; 2.5 mg/kg once) after intramuscular (IM), subcutaneous (SC), and slow intravenous (IV) administration to six adult horses. A three-phase design and 4-week washout period were used. Drug concentrations in blood and bronchoalveolar lavage (BAL) samples were determined by ultra-performance liquid chromatography tandem mass spectrometry and pharmacokinetic parameters calculated using noncompartmental analysis. Following SC and IM administration, all horses exhibited sweating, discomfort, and periods of recumbency. As signs were more severe after SC administration this route was only used in 3/6 horses. Intravenous administration of tulathromycin was well tolerated in all horses. Mean bioavailability was 99.4% IM and 115% SC. Mean maximum plasma concentration was 645 ng/ml IM and 373 ng/ml SC. Mean half-life was 59.8 h, 54.8 h, and 57.9 h for IV, IM, and SC administration, respectively. Mean clearance was 3.25 ml/kg/min, and mean volume of distribution was 16.8 L/kg following IV administration. Drug was detectable in plasma and BAL samples for 120 h following all routes; however, adverse effects may prevent IM use and SC use is not recommended. Tulathromycin may be a practical and affordable antimicrobial for use in adult equine patients.

摘要

本研究旨在确定 2.5mg/kg 土拉霉素(特拉美星;肌肉注射、皮下注射和缓慢静脉注射)后在 6 匹成年马中的药代动力学和耐受性。采用三相设计和 4 周洗脱期。采用超高效液相色谱串联质谱法测定血和支气管肺泡灌洗液(BAL)样本中的药物浓度,并采用非房室分析计算药代动力学参数。皮下和肌肉注射后,所有马均出现出汗、不适和卧倒期。由于皮下注射后症状更严重,因此只有 3/6 匹马使用此途径。所有马匹均耐受良好静脉注射土拉霉素。肌肉注射的平均生物利用度为 99.4%,皮下注射的平均生物利用度为 115%。肌肉注射的平均最大血浆浓度为 645ng/ml,皮下注射的平均最大血浆浓度为 373ng/ml。静脉、肌肉和皮下注射的平均半衰期分别为 59.8、54.8 和 57.9 小时。静脉注射后的平均清除率为 3.25ml/kg/min,平均分布容积为 16.8L/kg。所有途径给药后,均可在 120 小时内检测到血浆和 BAL 样本中的药物,但不良反应可能会阻止肌肉注射,且不建议皮下注射。土拉霉素可能是一种实用且经济实惠的成年马用抗菌药物。

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