In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). For veterinarians, taking into account the detection times of DIA and its active metabolites is needed for minimizing the risk of an anti-doping rule violation. Therefore, a pharmacokinetic study on 6 horses was conducted using a single intravenous (IV) dose of 0.2 mg/kg DIA Plasma and urine samples were collected at specified intervals until 16 and 26 days post-administration, respectively. Samples were analysed by a sensitive liquid chromatography–electrospray ionization/tandem mass spectrometry method. DIA showed a triphasic elimination pattern in the horse. The mean plasma clearance of DIA was 5.9 ml/min/kg, and the plasma elimination half-life in the terminal phase was 19.9 h. Applying the Toutain model approach, an effective plasma concentration of DIA was estimated at 24 ng/ml, and irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were computed to 0.047 and 0.1 ng/ml, respectively. The detection time according to the European Horserace Scientific Liaison Committee (EHSLC), that is the time for which observed DIA plasma concentrations of all investigated horses were below the IPC was 10 days. Using Monte Carlo Simulations, it was estimated that concentrations of DIA in plasma would fall below the IPC 18 days after the DIA administration for 90% of horses. However, in the present study, a single administration of DIA could be detected for 24 days in urine via the presence of OXA, its dominant metabolite.

中文翻译：

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马静脉注射地西泮后地西泮及其代谢物的动力学分布：兴奋剂控制的相关性

在马中，苯二氮卓类地西泮 (DIA) 用作给药前的镇静剂或用作抗焦虑剂以方便马检查。由于镇静作用也可能被滥用用于兴奋剂目的，因此在马运动中禁止使用 DIA。DIA 广泛代谢为几种活性代谢物，例如去甲西泮、替马西泮和奥沙西泮 (OXA)。对于兽医来说，需要考虑 DIA 及其活性代谢物的检测时间，以最大限度地降低违反反兴奋剂规则的风险。因此，使用 0.2 mg/kg DIA 的单次静脉内 (IV) 剂量对 6 匹马进行了药代动力学研究，分别在给药后 16 天和 26 天以指定的时间间隔收集血浆和尿液样本。通过灵敏的液相色谱-电喷雾电离/串联质谱法分析样品。DIA 显示马的三相消除模式。DIA 的平均血浆清除率为 5.9 ml/min/kg，末期血浆消除半衰期为 19.9 h。应用 Toutain 模型方法，DIA 的有效血浆浓度估计为 24 ng/ml，无关血浆浓度 (IPC) 和无关尿液浓度 (IUC) 分别计算为 0.047 和 0.1 ng/ml。根据欧洲赛马科学联络委员会 (EHSLC) 的检测时间，即观察到的所有研究马的 DIA 血浆浓度低于 IPC 的时间为 10 天。使用蒙特卡罗模拟，估计 90% 的马在 DIA 给药 18 天后血浆中的 DIA 浓度将低于 IPC。然而，在本研究中，