Dipyrone is a non-opioid, nonsteroidal anti-inflammatory drug with antipyretic and analgesic properties commonly used in horses. Dipyrone is rapidly hydrolyzed to the primary active metabolite 4-methylaminoantipyrine (4-MAA). The purpose of this study was to determine the pharmacokinetic profile of 4-MAA following repeated and escalating doses of intravenously administered dipyrone. Twenty-six horses were randomly allocated to five treatment groups (one placebo group and four dipyrone groups [30 mg/kg q8h, 30 mg/kg q12h, 60 mg/kg q8h, and 90 mg/kg q12h]) and treated for nine consecutive days. Blood was collected at predetermined timepoints, and plasma was analyzed for 4-MAA concentrations with a validated LC/MS/MS method. Following a single dose, there was a linear correlation to the maximum concentration (C_max) achieved. There was a disproportionate increase in the minimum concentration (C_min) of 4-MAA with accumulation occurring at higher doses or more frequent dosing intervals. Significant differences were noted in 4-MAA C_max, half-life, and area under the curve during the dosing interval (AUC_tau) when dipyrone was administered at 30 mg/kg q12h versus q8h. Adverse effects attributed to drug administration were not noted.

中文翻译：

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安乃近在马体内的药代动力学：多剂量、剂量递增研究

安乃近是一种非阿片类、非甾体类抗炎药，具有解热和镇痛作用，常用于马。安乃近快速水解为主要活性代谢物 4-甲氨基安替比林 (4-MAA)。本研究的目的是确定重复和递增剂量静脉注射安乃近后 4-MAA 的药代动力学特征。将 26 匹马随机分配到 5 个治疗组（1 个安慰剂组和 4 个安乃近组 [30 mg/kg q8h、30 mg/kg q12h、60 mg/kg q8h 和 90 mg/kg q12h]）并治疗 9 次。连续多日。在预定时间点采集血液，并使用经过验证的 LC/MS/MS 方法分析血浆中的 4-MAA 浓度。_{单剂量后，与达到的最大浓度 (C max} )呈线性相关。4-MAA 的最低浓度 (C _min )不成比例地增加，并且在较高剂量或更频繁的给药间隔下发生积累。当安乃近以 30 mg/kg 每 12 小时给药与每 8 小时给药时， 4-MAA C _max、半衰期和给药间隔期间曲线下面积 (AUC _tau )存在显着差异。没有注意到归因于给药的不良反应。