Department of Population Health and Pathobiology and the Food Animal Residue Avoidance and Depletion Program (FARAD), North Carolina State University, Raleigh 27607.
Department of Population Health and Pathobiology and the Food Animal Residue Avoidance and Depletion Program (FARAD), North Carolina State University, Raleigh 27607.
J Dairy Sci. 2022 Jan;105(1):549-559. doi: 10.3168/jds.2021-20460. Epub 2021 Oct 14.
Flunixin is a nonsteroidal anti-inflammatory drug approved for use in cattle to manage pyrexia associated with bovine respiratory disease, mastitis, and endotoxemia. In the United States, no nonsteroidal anti-inflammatory drugs are approved for use in goats, but analgesics are needed for management of painful conditions to improve animal welfare. The objective of this study was to evaluate the pharmacokinetics of transdermal flunixin in dairy goats to determine a milk withdrawal interval (WDI) to avoid violative residue contamination in the food supply. Six adult lactating dairy goats received 3.3 mg/kg of transdermal flunixin before milk, interstitial fluid (ISF), and blood samples were collected at various time points for 360 h. The samples were analyzed using tandem mass spectrometry to detect flunixin as well as the flunixin marker metabolite, 5-hydroxyflunixin followed by a pharmacokinetic WDI calculation using the US Food and Drug Administration tolerance limit method to propose safe residue levels in goat milk. The mean flunixin apparent plasma half-life was 21.63 h. The apparent milk half-life for 5-hydroxyflunixin was 17.52 h. Our findings provide a milk WDI of 60 h using the US Food and Drug Administration tolerance of 0.002 µg/mL (established for bovine milk) and a more conservative WDI of 96 h using a limit of quantification of 0.001 µg/mL following the extralabel use of transdermal flunixin in dairy goats.
氟尼辛是一种非甾体抗炎药，经批准可用于牛，以治疗与牛呼吸道疾病、乳腺炎和内毒素血症相关的发热。在美国，没有非甾体抗炎药被批准用于山羊，但为了管理疼痛状况以改善动物福利，需要使用镇痛药。本研究的目的是评估经皮氟尼辛在乳用山羊中的药代动力学，以确定一个牛奶停药期（WDI），以避免食品供应中出现违规残留污染。6 只成年泌乳山羊在挤奶前接受 3.3mg/kg 的经皮氟尼辛，然后在 360 小时内的不同时间点采集间质液（ISF）和血液样本。使用串联质谱法分析样品以检测氟尼辛以及氟尼辛标记代谢物 5-羟基氟尼辛，然后使用美国食品和药物管理局（FDA）容忍限度法进行药代动力学 WDI 计算，以提出山羊奶中的安全残留水平。氟尼辛的平均表观血浆半衰期为 21.63 小时。5-羟基氟尼辛的表观奶半衰期为 17.52 小时。我们的研究结果提供了一个牛奶 WDI，使用 FDA 容忍限度为 0.002µg/mL（为牛奶设定）为 60 小时，使用更保守的 WDI 为 96 小时，前提是经皮氟尼辛在乳用山羊中标签外使用。
