Mercer Melissa A, McKenzie Harold C, Byron Christopher R, Pleasant Robert S, Bogers Sophie H, Council-Troche Roberto M, Werre Stephen R, Burns Travis, Davis Jennifer L
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Equine Vet J. 2023 May;55(3):524-533. doi: 10.1111/evj.13601. Epub 2022 Jun 24.
Acetaminophen has been used clinically in horses alone or combined with traditional non-steroidal anti-inflammatory drugs for treatment of musculoskeletal pain in horses.
To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control.
In vivo experiment.
Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2 mg/kg, PO; PB) and oral placebo (C) in a randomised four-way Latin square model. Plasma concentrations for A20 and A30 were analysed via LC-MS/MS and noncompartmental pharmacokinetic analysis. Heart rate and heart rate variability were measured using a portable telemetry. Lameness was scored by three blinded boarded equine surgeons using the AAEP and 10-point scales.
Mean maximum plasma concentration (C ) for A20 was 20.01 μg/ml within 0.66 h (T ) after administration; The mean C for A30 was 30.02 μg/ml with a T of 0.43 h. Post-treatment heart rate for A30 was significantly lower than A20 at 1 and 7 h; lower than PB at 2, 3, 4.5 and 7 h; lower than C at 2, 3.5, 4.5, 6, 7 and 8 h. 10-point Lameness scores were significantly improved for A30 than C at 2 and 4 h post-treatment; PB was significantly improved than C at 8 h post treatment. There were no significant differences in lameness between A20, A30 and PB.
Small sample size, lack of objective lameness measurement.
Acetaminophen at 30 mg/kg produced a more rapid improvement in lameness scores and heart rate compared with other treatments in this model. Further evaluation of the pharmacokinetics and safety of repeated oral dosing of acetaminophen at 30 mg/kg is needed to determine clinical utility.
对乙酰氨基酚已在临床上单独用于马匹，或与传统非甾体抗炎药联合用于治疗马匹的肌肉骨骼疼痛。
与苯基布他松或安慰剂对照相比，确定两种剂量的对乙酰氨基酚在机械性诱导跛行马匹中的药代动力学和疗效。
体内实验。
通过可逆性蹄底压力马蹄模型诱导出机械性跛行的9匹健康母马，采用随机四向拉丁方模型，分别用对乙酰氨基酚（20mg/kg口服；A20）、对乙酰氨基酚（30mg/kg口服；A30）、苯基布他松（2.2mg/kg，口服；PB）和口服安慰剂（C）进行治疗。通过液相色谱-串联质谱法和非房室药代动力学分析对A20和A30的血浆浓度进行分析。使用便携式遥测仪测量心率和心率变异性。由三名不知情的注册马外科医生使用美国马术从业者协会（AAEP）评分标准和10分制对跛行进行评分。
A20给药后0.66小时（Tmax）的平均最大血浆浓度（Cmax）为20.01μg/ml；A30的平均Cmax为30.02μg/ml，Tmax为0.43小时。A30治疗后的心率在1小时和7小时显著低于A20；在2小时、3小时、4.5小时和7小时低于PB；在2小时、3.5小时、4.5小时、6小时、7小时和8小时低于C。治疗后2小时和4小时，A30的10分制跛行评分比C显著改善；治疗后8小时，PB比C显著改善。A20、A30和PB之间的跛行情况无显著差异。
样本量小，缺乏客观的跛行测量方法。
在该模型中，与其他治疗方法相比，30mg/kg的对乙酰氨基酚在改善跛行评分和心率方面起效更快。需要进一步评估30mg/kg对乙酰氨基酚重复口服给药的药代动力学和安全性，以确定其临床效用。
