There is currently little information available on the pharmacokinetics and pharmacodynamics of the analgesic opioid tramadol when used in the veterinary medicine of domestic species. In this study, we aimed to determine the pharmacokinetics of tramadol and its active metabolite M1 following intravenous administration of 2 (T2) and 4 (T4) mg/kg to Northeast Brazilian donkeys. Tramadol and M1 plasma levels were quantified using a validated liquid chromatography–tandem mass spectrometry method. We found that plasma levels of tramadol and M1 were higher than those reported as clinically meaningful in humans for at least 3 hr. However, the pharmacokinetic parameter calculation corrected by dose analysis identified no proportional increase with dose for the AUC of tramadol (T2: 2,663 ± 1,827 vs. T4: 2,964 ± 1,038 ng*h/ml) and M1 (T2: 378 ± 237 vs. T4: 345 ± 142 ng*h/ml). This finding appears to be attributable to a significant increase in clearance and a reduction in the terminal half-life of tramadol. The frequency of adverse effects observed at the higher dose indicates that 2 mg/kg administered intravenously would be suitable for donkeys. Clinical studies are required to determine the implications of these observations regarding the pharmacodynamic response to tramadol in Northeast Brazilian donkeys.

中文翻译：

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曲马多和 M1 代谢物在巴西东北驴 (Equus asinus) 中的药代动力学特性

目前关于镇痛剂曲马多用于国内物种的兽药时的药代动力学和药效学信息很少。在本研究中，我们旨在确定向巴西东北部驴静脉注射 2 (T2) 和 4 (T4) mg/kg 后曲马多及其活性代谢物 M1 的药代动力学。使用经过验证的液相色谱-串联质谱法对曲马多和 M1 血浆水平进行量化。我们发现曲马多和 M1 的血浆水平高于在人类中报告的具有临床意义的至少 3 小时。然而，通过剂量分析校正的药代动力学参数计算发现曲马多的 AUC（T2：2,663 ± 1,827 与 T4：2,964 ± 1,038 ng*h/ml）和 M1（T2：378 ± 237 与T4：345 ± 142 纳克*小时/毫升）。这一发现似乎归因于曲马多的清除率显着增加和终末半衰期缩短。在较高剂量下观察到的不良反应频率表明静脉内给药 2 mg/kg 适合驴。需要临床研究来确定这些观察结果对巴西东北部驴对曲马多的药效学反应的影响。