Metamizole (MT), also known as dipyrone, is an analgesic and antipyretic drug labeled for use in humans and domestic animals in some countries. As with other drugs, the administration of MT in donkeys is based on studies carried out with horses. In the present report, we aimed to determine the pharmacokinetics of the two main metamizole active metabolites (N-methyl-4-aminoantipyrine [MAA] and 4-aminoantipyrine [AA]) following 10 (M₁₀) and 25 mg/kg (M₂₅) IV metamizole doses in Northeast Brazilian donkeys (n = 10). Blood was collected at predetermined times within over 48 h; MAA and AA plasma concentrations were determined by a validated LC-MS/MS method. The metabolites were quantifiable in the M₁₀ until 12 h and M₂₅ until 24 h after drug administration. As expected, AUC_0→t, AUC_0→∞, and C_max demonstrated significant differences increases in metamizole metabolites profiles when groups were compared. No adverse effects were observed. This study indicates the need for an extremely sensitive analytical method to adequately characterize the pharmacokinetics of active metabolites of MT, MAA, and AA. In conclusion, the method developed in this research was able to measure the active metabolites of metamizole and with that it was possible to establish their pharmacokinetic profile. Furthermore, after projection of the minimum MAA concentrations, it is possible to infer that the dose of 10 mg/kg will be used on donkeys at 6 h intervals, while the M25 group at 12 h intervals. However, clinical studies are needed to assess this hypothesis.

中文翻译：

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巴西东北部驴（Equus asinus）安乃近活性代谢物的药代动力学特性

安乃近 (MT)，也称为安乃近，是一种镇痛和解热药物，在一些国家标记为用于人类和家畜。与其他药物一样，在驴中使用 MT 是基于对马进行的研究。在本报告中，我们旨在确定在 10 (M ₁₀ ) 和 25 mg/kg (M ₂₅ ) 巴西东北部驴 ( n  = 10) 的 IV 安乃近剂量。在超过 48 小时内按预定时间采集血液；MAA 和 AA 血浆浓度通过经过验证的 LC-MS/MS 方法确定。代谢物在 M ₁₀至 12 小时和 M _{25中可量化}直至给药后24小时。正如所料，AUC _0→t、AUC _0→∞和 C _max当比较组时，证明了安乃近代谢物谱的显着差异增加。没有观察到不良反应。这项研究表明需要一种极其灵敏的分析方法来充分表征 MT、MAA 和 AA 的活性代谢物的药代动力学。总之，本研究中开发的方法能够测量安乃近的活性代谢物，从而有可能建立它们的药代动力学特征。此外，在推算出最低 MAA 浓度后，可以推断出 10 mg/kg 的剂量将每隔 6 小时用于驴，而 M25 组每隔 12 小时使用一次。然而，需要临床研究来评估这一假设。