Repeated administration of meloxicam to cats is often limited by the potential damage to multiple organ systems. Identifying molecules that predict the adverse effects of meloxicam would help to monitor and individualize its administration, maximizing meloxicam's beneficial effects. The objectives of this study were to (a) determine if the repeated administration of meloxicam to cats alters the plasma metabolome and (b) identify plasma metabolites that may serve to monitor during the administration of meloxicam in cats. Purpose bred young adult cats (n = 12) were treated with meloxicam at 0.3 mg/kg or saline subcutaneously once daily for up to 17 days. An untargeted metabolomics approach was applied to plasma samples collected prior to and at designated time points after meloxicam or saline administration. To refine the discovery of biomarkers, the machine‐learning algorithms, partial least squares discriminant analysis (PLS‐DA) and random forest (RF), were trained and validated using a separate unrelated group of meloxicam‐ and saline‐treated cats (n = 8). A total of 74 metabolites were included in the statistical analysis. Metabolomic analysis shows that the repeated administration of meloxicam alters multiple substances in plasma, including nonvolatile organic acids, aromatic amino acids, monosaccharides, and inorganic compounds as early as four days following administration of meloxicam. Seventeen plasma molecules were able to distinguish meloxicam‐treated from saline‐treated cats. The metabolomic changes discovered in this study may help to unveil unknown mechanisms of NSAID‐induced side effects. In addition, some metabolites could be valuable for individualizing the administration of meloxicam to cats to mitigate adverse effects.

中文翻译：

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药代动力学结合PLS-DA和随机森林算法分析显示，美洛昔康改变猫血浆代谢物谱。

对猫重复服用美洛昔康通常受到对多个器官系统潜在损害的限制。鉴定预测美洛昔康不良作用的分子将有助于监测和个性化其给药，从而最大化美洛昔康的有益作用。这项研究的目的是（a）确定是否向猫重复服用美洛昔康是否会改变血浆代谢物，（b）确定在猫中服用美洛昔康期间可能用于监测的血浆代谢物。目的繁殖的成年幼猫（n = 12）每天一次以0.3 mg / kg的美洛昔康或盐水皮下注射一次，最多治疗17天。将非靶向代谢组学方法应用于在服用美洛昔康或生理盐水之前和之后的指定时间点收集的血浆样品。为了完善生物标志物的发现，机器学习算法，偏最小二乘判别分析（PLS‐DA）和随机森林（RF）经过培训，并使用了单独的一组无关的美洛昔康和盐处理的猫（n = 8）。统计分析中总共包括74种代谢物。代谢组学分析表明，在服用美洛昔康后四天，重复服用美洛昔康会改变血浆中的多种物质，包括非挥发性有机酸，芳香族氨基酸，单糖和无机化合物。十七种血浆分子能够区分用美洛昔康治疗和盐水治疗的猫。在这项研究中发现的代谢组学变化可能有助于揭示NSAID诱导的副作用的未知机制。此外，某些代谢物可能对于个性化美洛昔康对猫的给药以减轻不良影响可能很有价值。