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Comparative Pharmacokinetics of Meloxicam Between Healthy Post-partum vs. Mid-lactation Dairy Cattle
Frontiers in Veterinary Science ( IF 2.6 ) Pub Date : 2020-07-13 , DOI: 10.3389/fvets.2020.00548
Rochelle Warner , Joshua A. Ydstie , Larry W. Wulf , Ronette Gehring , Johann F. Coetzee , Jonathan P. Mochel , Patrick J. Gorden

Lactating dairy cattle are at risk for various painful conditions throughout their life, such as lameness, parturition, mastitis, and metabolic disorders. These conditions necessitate adequate methods of analgesia to address welfare concerns through efficacious pain mitigation. As no method of analgesia has been approved for lactating dairy cattle, to date, research is necessary to determine effective pain management strategies for dairy cattle. In both the European Union and Canada, meloxicam has been approved for use in lactating dairy cattle as a methodology for pain control. The objective of this study was to characterize the pharmacokinetics of meloxicam administered orally and intravenously to lactating dairy cattle in the post-partum vs. mid-lactation period. In this parallel study design, 12 healthy, lactating Holsteins were enrolled within 24 h of freshening and randomly allocated to intravenous (0.2 mg/kg) or oral (1.0 mg/kg) meloxicam administration treatment groups. They were matched based on parity to 12, healthy cows that were considered mid-lactation [>150 days-in-milk (DIM)] to receive the same treatment. Based on meloxicam formulation, sampling times varied and plasma was collection via jugular venipuncture for 6 days. Plasma drug concentrations were evaluated using liquid chromatography coupled with mass spectroscopy and pharmacokinetic properties were evaluated using non-compartmental (i.e., statistical moments) analysis. Results indicated a decreased systemic clearance of meloxicam in post-partum relative to mid-lactation cows, which resulted in a longer half-life and increased total exposure independent of mode of administration. These results suggest a need for dose adjustments based on stage in lactation and further assessment of the impact of days-in-milk on milk withholding period.



中文翻译:

健康产后牛与泌乳中期牛之间美洛昔康的比较药代动力学

泌乳的奶牛一生面临各种痛苦状况的危险,例如la行,分娩,乳腺炎和代谢紊乱。这些情况需要采取适当的镇痛方法,以通过有效的缓解疼痛来解决福利问题。由于至今尚未批准用于哺乳奶牛的镇痛方法,因此有必要进行研究以确定奶牛的有效疼痛管理策略。在欧盟和加拿大,美洛昔康已被批准用于泌乳奶牛,作为控制疼痛的方法。这项研究的目的是表征产后与哺乳中期对哺乳奶牛口服和静脉内服用美洛昔康的药代动力学。在这项平行研究设计中,有12位健康的人,哺乳期的荷斯坦牛在新鲜后24小时内入组,随机分配给静脉注射(0.2 mg / kg)或口服(1.0 mg / kg)的美洛昔康给药治疗组。根据同等比例将它们匹配到12头健康母牛,这些母牛被认为是哺乳中期[> 150乳日(DIM)]以接受相同的治疗。根据美洛昔康的配方,采样时间会有所变化,并通过颈静脉穿刺收集血浆6天。使用液相色谱结合质谱法评估血浆药物浓度,并使用非房室(即统计矩)分析评估药代动力学特性。结果表明,与哺乳中期的母牛相比,美洛昔康在产后的全身清除率降低,导致更长的半衰期和增加的总暴露量,而与给药方式无关。这些结果表明,需要根据泌乳阶段调整剂量,并进一步评估母乳日数对禁奶期的影响。

更新日期:2020-09-09
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