1Department of Population Health and Pathobiology and the Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.
J Am Vet Med Assoc. 2023 Sep 21;261(12):1873-1879. doi: 10.2460/javma.23.06.0329. Print 2023 Dec 1.
To determine the influence of stage of lactation on the pharmacokinetics in milk when multiple doses of meloxicam were administered alone or in combination with gabapentin to postpartum (PP) and mid-lactation (ML) cows.
8 postpartum and 8 mid-lactation dairy cows.
Cows were randomly divided into 2 groups (n = 8) which included 4 PP cows and 4 ML cows. Group I received only 6 oral daily doses of meloxicam (1.0 mg/kg for 6 doses). Group II received 6 oral daily doses of co-administered meloxicam (1.0 mg/kg) and gabapentin (20 mg/kg) for 6 doses. Meloxicam and gabapentin were quantified in plasma and milk samples by ultra-high-performance liquid chromatography-tandem mass spectrometry, and the pharmacokinetic analysis of milk and plasma was performed using a non-compartmental approach.
Regardless of lactation status, dairy cattle administered multiple doses of meloxicam and/or gabapentin showed low drug residue concentrations and little accumulation in milk. The terminal plasma half-life of meloxicam was significantly increased (P < .02) in PP cows (12.9 hr) compared to ML cows (9.4 hr). The apparent terminal half-life in milk for meloxicam and gabapentin was not affected by stage of lactation. Co-administration of gabapentin did not alter plasma or milk concentrations of meloxicam.
The results of this study suggest that milk from cows treated with multiple doses of meloxicam alone or in combination with gabapentin will have low drug concentrations and falls below our reported limit of detection for meloxicam or gabapentin 120 and 60 hours respectively, following the final dose regardless of their stage of lactation.
确定哺乳期阶段对多次给予美洛昔康单独或与加巴喷丁联合给药后牛奶中药物动力学的影响。
8 头产后和 8 头泌乳中期奶牛。
奶牛随机分为 2 组(n = 8),包括 4 头产后奶牛和 4 头泌乳中期奶牛。第 1 组仅接受 6 次口服美洛昔康(6 次剂量为 1.0 mg/kg)。第 2 组接受 6 次口服联合美洛昔康(1.0 mg/kg)和加巴喷丁(20 mg/kg)共 6 次剂量。通过超高效液相色谱-串联质谱法对血浆和牛奶样本中的美洛昔康和加巴喷丁进行定量,并采用非房室模型进行牛奶和血浆的药代动力学分析。
无论泌乳状态如何,多次给予美洛昔康和/或加巴喷丁的奶牛牛奶中药物残留浓度低且蓄积少。与泌乳中期奶牛(9.4 小时)相比,产后奶牛(12.9 小时)中美洛昔康的终末血浆半衰期明显延长(P <.02)。美洛昔康和加巴喷丁在牛奶中的表观终末半衰期不受泌乳阶段的影响。加巴喷丁的合并给药并未改变美洛昔康的血浆或牛奶浓度。
本研究结果表明,多次给予美洛昔康单独或与加巴喷丁联合治疗的奶牛的牛奶中药物浓度较低,在末次给药后 120 小时和 60 小时分别低于我们报道的美洛昔康和加巴喷丁的检测限,无论其泌乳阶段如何。