Comparative Pharmacokinetics of Meloxicam between Healthy Post-partum versus Mid-lactation Dairy Cattle

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 six 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

泌乳奶牛在整个生命周期中面临多种疼痛性病症风险，例如跛行、分娩、乳腺炎及代谢紊乱。此类病症亟需采用合适的镇痛手段，通过有效缓解疼痛以改善动物福利。截至目前，尚无获批用于泌乳奶牛的镇痛疗法，因此亟需开展相关研究以确定切实有效的奶牛疼痛管理策略。在欧盟与加拿大境内，美洛昔康（meloxicam）已获批作为泌乳奶牛的疼痛控制用药。本研究旨在对比产后与泌乳中期泌乳奶牛经口及静脉给予美洛昔康后的药代动力学特征。本研究采用平行组实验设计，将12头健康泌乳荷斯坦奶牛（Holsteins）在分娩后24小时内纳入实验，随机分为静脉给药组（0.2 mg/kg）与口服给药组（1.0 mg/kg）。同时按照胎次匹配12头健康泌乳中期奶牛（泌乳天数>150天，days-in-milk, DIM），使其接受相同的给药处理。根据美洛昔康的制剂规格调整采样时间，通过颈静脉穿刺采血连续6天采集血浆样本。采用液相色谱-质谱联用法（liquid chromatography coupled with mass spectroscopy）测定血浆药物浓度，并采用非房室模型（即统计矩法）分析药代动力学参数。研究结果显示，与泌乳中期奶牛相比，产后奶牛的美洛昔康全身清除率降低，进而导致药物半衰期延长、总暴露量增加，且该差异与给药途径无关。上述结果提示，需根据泌乳阶段调整给药剂量，并需进一步评估泌乳天数对牛奶休药期的影响。