K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Equine Vet J. 2021 Jan;53(1):102-116. doi: 10.1111/evj.13260. Epub 2020 Apr 17.
Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects.
Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators.
Two-way randomised balanced crossover experiment.
Twelve Thoroughbred exercised horses received 500 mg FM IV alone or in combination with 2 g of IV PBZ 24 hours later. Blood and urine samples were collected prior to and for up to 120 hours post-drug administration. Whole blood samples were collected at various times and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of FM, PBZ and eicosanoids were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis performed on concentration data.
Flunixin meglumine clearance was significantly increased when horses received PBZ 24 hours post-administration (P = .03). No other differences in pharmacokinetic parameters were noted between groups. Thromboxane B was significantly suppressed, relative to baseline for 96 hours post-FM administration. Subsequent administration of PBZ prolonged the suppression. Prostaglandin E2 was decreased for 24 hours following administration of FM with subsequent administration of PBZ prolonging the suppression until 120 hours. PGF concentrations were decreased for up to 168 hours post-FM administration. FM administration significantly decreased 15-HETE.
Small sample size and lack of a phenylbutazone-only treatment group.
Administration of PBZ post-FM administration increased FM clearance. The anti-inflammatory effects of FM appear to be prolonged when PBZ is administered 24 hours post-administration.
氟尼辛甲胺（FM）和苯丁唑酮（PBZ）是强效抗炎药，因此它们有可能掩盖原本会导致马匹无法训练或比赛的损伤，这令人担忧。在美国，赛道医学中的一种常见做法是在彼此相距很近的时间（24 小时内）内同时使用这两种药物，这引起了对药代动力学相互作用和增强抗炎作用的关注。
描述当 FM 与 PBZ 近距离给药时 PBZ 对 FM 清除率的影响以及对炎症介质的影响。
双向随机平衡交叉实验。
12 匹纯种运动马单独接受 500mg IV FM 或在 24 小时后接受 2g IV PBZ 联合治疗。在给药前和给药后长达 120 小时内采集血样和尿样。在不同时间采集全血样本，并使用脂多糖或钙离子载体刺激，以诱导花生四烯酸的体外合成。使用 LC-MS/MS 测量 FM、PBZ 和花生四烯酸的浓度，并对浓度数据进行非房室药代动力学分析。
当马匹在给药后 24 小时接受 PBZ 治疗时，FM 清除率显著增加（P = 0.03）。两组之间没有观察到其他药代动力学参数的差异。与 FM 给药后基线相比，血栓烷 B 在 96 小时内显著被抑制。随后给予 PBZ 延长了抑制作用。FM 给药后 24 小时内前列腺素 E2 减少，随后给予 PBZ 直至 120 小时延长了抑制作用。PGF 浓度在 FM 给药后长达 168 小时内降低。FM 给药显著降低了 15-HETE。
样本量小且缺乏单独使用苯丁唑酮的治疗组。
FM 给药后给予 PBZ 增加了 FM 的清除率。当 PBZ 在给药后 24 小时内给予时，FM 的抗炎作用似乎会延长。
