Nixon Emma, Almond Glen W, Baynes Ronald E, Messenger Kristen M
Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Front Vet Sci. 2020 Feb 20;7:82. doi: 10.3389/fvets.2020.00082. eCollection 2020.
Piglet castration and tail-docking are routinely performed in the United States without analgesia. Pain medications, predominately non-steroidal anti-inflammatory drugs, are used in the EU/Canada to decrease pain associated with processing and improve piglet welfare, however, past studies have shown the efficacy and required dose remain controversial, particularly for meloxicam. This study assessed the pharmacokinetics of three NSAIDs (meloxicam, flunixin, and ketoprofen) in piglets prior to undergoing routine castration and tail-docking. Five-day-old male piglets (8/group) received one of 3 randomized treatments; meloxicam (0.4 mg/kg), flunixin (2.2 mg/kg), ketoprofen (3.0 mg/kg). Two hours post-dose, piglets underwent processing. Drug concentrations were quantified in plasma and interstitial fluid (ISF) and pharmacokinetic parameters were generated by non-compartmental analysis. Time to peak concentration (T) of meloxicam, flunixin, and S(-)-ketoprofen in plasma were 1.21, 0.85, and 0.59 h, compared to 2.81, 3.64, and 2.98 h in the ISF, respectively. The apparent terminal half-life of meloxicam, flunixin and S(-)-ketoprofen were 4.39, 7.69, and 3.50 h, compared to 11.26, 16.34, and 5.54 h, respectively in the ISF. If drug concentrations in the ISF are more closely related to efficacy than the plasma, then the delay between the Tmax in plasma and ISF may be relevant to the timing of castration in order to provide the greatest analgesic effect.
在美国,仔猪去势和断尾通常在没有镇痛措施的情况下进行。在欧盟/加拿大,主要使用非甾体抗炎药等止痛药物来减轻与屠宰过程相关的疼痛并改善仔猪福利,然而,过去的研究表明其疗效和所需剂量仍存在争议,尤其是美洛昔康。本研究评估了三种非甾体抗炎药(美洛昔康、氟尼辛和酮洛芬)在仔猪进行常规去势和断尾前的药代动力学。5日龄雄性仔猪(每组8只)接受3种随机处理之一;美洛昔康(0.4mg/kg)、氟尼辛(2.2mg/kg)、酮洛芬(3.0mg/kg)。给药后2小时,仔猪接受屠宰处理。对血浆和组织间液(ISF)中的药物浓度进行定量,并通过非房室分析生成药代动力学参数。美洛昔康、氟尼辛和S(-)-酮洛芬在血浆中的达峰时间(T)分别为1.21、0.85和0.59小时,而在ISF中分别为2.81、3.64和2.98小时。美洛昔康、氟尼辛和S(-)-酮洛芬的表观末端半衰期分别为4.39、7.69和3.50小时,而在ISF中分别为11.26、16.34和5.54小时。如果ISF中的药物浓度比血浆中的浓度与疗效更密切相关,那么血浆和ISF中Tmax之间的延迟可能与去势时间有关,以便提供最大的镇痛效果。