BACKGROUND The increasing prevalence of xylazine in the illicit drug supply is a growing concern for major health consequences in individuals who use fentanyl mixed with xylazine, but limited data are available regarding the pharmacokinetics of xylazine in humans. METHODS Xylazine was quantified in serial remnant plasmas collected from 28 patients starting at the initial patient encounter and continuing for up to 52 h from presentation, using LC-MS/MS to calculate the terminal half-life for xylazine. Xylazine metabolites were identified by product ion scanning, and multiple reaction monitoring was used to estimate the relative abundance of xylazine metabolites in 74 collected plasma samples. RESULTS The median terminal half-life for xylazine was calculated to be 12.0 h (range: 5.9-20.8). Oxo-xylazine and sulfone-xylazine metabolites were detected in all plasma specimens that contained xylazine. CONCLUSIONS The half-life of xylazine in humans is longer than previously observed in animal studies, which furthers the current understanding of the expected duration of effects in individuals who use fentanyl mixed with xylazine and the window of detection. Both oxo-xylazine and sulfone-xylazine appear to circulate in plasma for as long as xylazine.

中文翻译：

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芬太尼和甲苯噻嗪检测呈阳性的患者的甲苯噻嗪药代动力学。


背景 甲苯噻嗪在非法药物供应中日益普遍，这越来越令人担忧使用芬太尼与甲苯噻嗪混合的个体的重大健康后果，但关于甲苯噻嗪在人类中的药代动力学的数据有限。方法 使用 LC-MS/MS 计算甲苯噻嗪的终末半衰期，从 28 例患者初次就诊开始，持续 52 小时，对 28 例患者收集的连续残余血浆中甲苯噻嗪进行定量。通过子离子扫描鉴定甲苯噻嗪代谢物，并采用多反应监测估计 74 份收集的血浆样品中甲苯噻嗪代谢物的相对丰度。结果 计算出甲苯噻嗪的中位终末半衰期为 12.0 小时 （范围： 5.9-20.8）。在所有含有甲苯噻嗪的血浆标本中检测到氧代甲苯噻嗪和砜-甲苯噻嗪代谢物。结论甲苯噻嗪在人类中的半衰期比以前在动物研究中观察到的要长，这进一步加深了目前对使用芬太尼与甲苯噻嗪混合的个体的预期效果持续时间和检测窗口的理解。氧代甲苯噻嗪和砜-甲苯噻嗪在血浆中循环的时间似乎与甲苯噻嗪一样长。