Introduction: The study objectives were to estimate plasma flunixin (FLU) pharmacokinetic parameters and milk depletion profiles for FLU and its metabolite (5-hydroxy flunixin; 5-OH) after subcutaneous (SC) and intravenous (IV) administration of single and multiple flunixin meglumine (FM) doses to non-lactating (nulliparous and pregnant does) and lactating dairy goats. Analytical methods (ELISA and UPLC-MS/MS) for quantifying plasma FLU concentrations were compared. The final objective was to use regulatory (FDA and EMA) methods to estimate milk withdrawal intervals following extra-label drug use in goats. Methods: FM was administered IV and SC to commercial dairy goats at 1.1 mg/kg for single and multiple doses. Plasma and milk samples were analyzed for FLU and 5-OH via UPLC-MS/MS. Plasma samples were also analyzed for FLU concentrations via ELISA. Using statistical approaches recommended by regulatory agencies, milk withdrawal intervals were estimated following FM extra-label use. Results: Following IV administration of a single FM dose, clearances were 127, 199, and 365 ml/kg/h for non-lactating (NL) pregnant does, NL nulliparous does, and lactating dairy does, respectively. Following multiple SC doses, clearance/F was 199 ml/kg/h for lactating does. After IV administration of a single FM dose, terminal elimination half-lives were 4.08, 2.87, and 3.77 h for NL pregnant does, NL nulliparous does, and lactating dairy does, respectively. After multiple SC doses, the terminal elimination half-life was 3.03 h for lactating dairy does. No significant differences were noted for samples analyzed by UPLC-MS/MS or ELISA. Milk withdrawal intervals ranged from 36 to 60 h depending on the regulatory statistical method and dosage regimen. Conclusions: Subcutaneous administration of FM to goats results in similar plasma pharmacokinetic parameters as IV administration. ELISA analysis is an alternative method to UPLC-MS/MS for quantifying FLU concentrations in caprine plasma samples. Following FM extra-label administration to dairy goats, clinicians could consider 36-60 h milk withdrawal intervals.

中文翻译：

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氟尼辛葡甲胺单次和多次静脉内和皮下给药后，家山羊（Capra Aegagrus Hircus）的药代动力学参数和估计的吸奶间隔。

简介：研究目的是估计皮下注射（SC）和静脉内注射（静脉注射）氟尼辛后血浆氟尼辛（FLU）的药代动力学参数和FLU及其代谢产物（5-羟基氟尼辛； 5-OH）的牛奶消耗曲线葡甲胺（FM）剂量用于非哺乳期（哺乳山羊和哺乳山羊）。比较了定量血浆FLU浓度的分析方法（ELISA和UPLC-MS / MS）。最终目标是使用监管（FDA和EMA）方法来估计山羊使用标签外药物后的停奶间隔。方法：以1.1 mg / kg的单剂量和多剂量，对商业奶山羊进行FM和SC的FM施用。通过UPLC-MS / MS分析血浆和牛奶样品中的FLU和5-OH。还通过ELISA分析血浆样品的FLU浓度。使用监管机构建议的统计方法，在使用FM额外标签后估算停奶间隔。结果：在单次FM剂量的IV给药后，非哺乳期（NL）的孕妇，NL胎腹和哺乳期的乳品的清除率分别为127、199和365 ml / kg / h。在多次SC剂量下，泌乳的清除率/ F为199 ml / kg / h。静脉注射单次FM剂量后，NL怀孕，NL胎生和泌乳奶牛的终末消除半衰期分别为4.08、2.87和3.77 h。在多次SC剂量后，泌乳乳制品的最终消除半衰期为3.03小时。通过UPLC-MS / MS或ELISA分析的样品未发现明显差异。停奶间隔时间为36至60小时，具体取决于监管统计方法和剂量方案。结论：对山羊皮下注射FM所产生的血浆药代动力学参数与静脉注射相似。ELISA分析是UPLC-MS / MS定量血浆样品中FLU浓度的另一种方法。在对奶山羊进行FM超标签给药后，临床医生可以考虑停奶间隔36-60小时。