Department of Animal Pathology, Division of Veterinary Pharmacology and Toxicology, University of Turin, Italy.
Res Vet Sci. 2013 Aug;95(1):204-11. doi: 10.1016/j.rvsc.2013.01.018. Epub 2013 Feb 19.
The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral meloxicam (1mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, meloxicam and gabapentin were 6.0 h (range, 3.4-11.0 h), 16.7h (range, 13.7-21.3h) and 15.3h (range, 11-32.9h), respectively. The co-administration of single doses of gabapentin and meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P<0.05) higher maximum serum concentration (Cmax) when co-administered with meloxicam, than when administered alone. At 5, 360 and 720 min after dehorning, a significant (P<0.01) decrease in PGE2 concentration was observed in flunixin-treated animals compared with control calves. Moreover, circulating log PGE2 concentrations were inversely proportional to log flunixin concentrations (R(2)=0.75; P<0.0001). None of the other drugs significantly affected blood PGE2 levels. Further assessment of oral meloxicam and gabapentin in established pain models is required to formulate science based analgesic recommendations to enhance animal well-being after dehorning.
本研究旨在研究静脉注射氟尼辛（2.2mg/kg 体重）、口服美洛昔康（1mg/kg 体重）、口服加巴喷丁（15mg/kg 体重）单独或与美洛昔康联合使用时的药代动力学，以及这些化合物对去角后犊牛前列腺素 E2（PGE2）合成的影响。给药后长达 24 小时采集的血浆样品通过液相色谱/质谱法进行分析，而血液 PGE2 水平则通过免疫酶测定法进行测量。在血浆中，氟尼辛、美洛昔康和加巴喷丁的终末半衰期分别为 6.0 小时（范围 3.4-11.0 小时）、16.7 小时（范围 13.7-21.3 小时）和 15.3 小时（范围 11-32.9 小时）。单次给予加巴喷丁和美洛昔康似乎不会影响两种药物的药代动力学特征，除了加巴喷丁与美洛昔康联合使用时，达到显著更高的最大血清浓度（Cmax）（P<0.05）。去角后 5、360 和 720 分钟，与对照犊牛相比，氟尼辛治疗动物的 PGE2 浓度显著（P<0.01）降低。此外，循环 PGE2 浓度与氟尼辛浓度呈负相关（R2=0.75；P<0.0001）。其他药物均未显著影响血液 PGE2 水平。需要进一步评估口服美洛昔康和加巴喷丁在既定疼痛模型中的应用，以制定基于科学的镇痛建议，提高去角后动物的福利。
