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对给纯种马注射赛拉嗪的药代动力学的重新评估。

Re-evaluation of the pharmacokinetics of xylazine administered to Thoroughbred horses.

作者信息

Habershon-Butcher Jocelyn, Cutler Charlotte, Viljanto Marjaana, Hincks Pamela R, Biddle Simon, Paine Stuart W

机构信息

British Horseracing Authority, London, UK.

LGC, Fordham, UK.

出版信息

J Vet Pharmacol Ther. 2020 Jan;43(1):6-12. doi: 10.1111/jvp.12820. Epub 2019 Oct 25.

Abstract

Xylazine is widely used worldwide as a short-acting sedative in general equine and racing practice. In the UK, although it has a legitimate use during training, equine anti-doping rules state it is a prohibited substance on race day. The aim of the study was to produce a detection time (DT) to better inform European veterinary surgeons so that xylazine can be used appropriately under regulatory rules. Previous publications have various limitations pertaining to analysis method, particularly for plasma and limited length of time of sample collection. In this study, pharmacokinetic data were produced for xylazine and 4-OH-xylazine in equine urine and plasma following a single intravenous xylazine dose of 0.4 mg/kg to six Thoroughbred horses. Pharmacokinetic parameters were generated from a 3-compartmental model with clearance = 15.8 ± 4.88 ml min  kg , Vss = 1.44 ± 0.38 L/kg, terminal half-life = 29.8 ± 12.7 hr and a DT determined at 71 hr for the administration of xylazine (Chanazine ) in plasma and urine. Urine screening should aim to detect the 4-OH-xylazine metabolite, which can act as an indicator for the xylazine plasma concentration. A DT of 72 hr has been agreed by the European Horserace Scientific Liaison Committee, to be implemented in June 2019.

摘要

赛拉嗪在全球范围内广泛用作马类常规和赛马实践中的短效镇静剂。在英国,尽管它在训练期间有合法用途,但马类反兴奋剂规则规定在比赛日它是违禁物质。该研究的目的是确定一个检测时间(DT),以便更好地为欧洲兽医提供信息,从而使赛拉嗪能够在监管规则下得到适当使用。以往的出版物在分析方法方面存在各种局限性,特别是对于血浆以及样本采集时间有限。在本研究中,对6匹纯种马静脉注射0.4mg/kg的赛拉嗪后,测定了马尿和血浆中赛拉嗪及4-羟基赛拉嗪的药代动力学数据。药代动力学参数由三室模型得出,清除率=15.8±4.88ml·min·kg,稳态分布容积=1.44±0.38L/kg,末端半衰期=29.8±12.7小时,血浆和尿液中赛拉嗪(氯胺嗪)给药的检测时间确定为71小时。尿液筛查应旨在检测4-羟基赛拉嗪代谢物,它可作为赛拉嗪血浆浓度的指标。欧洲赛马科学联络委员会已商定检测时间为72小时,将于2019年6月实施。

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