Department of Clinical Sciences, Auburn University, Auburn, AL.
Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL.
Am J Vet Res. 2022 Jun 20;83(8):ajvr.21.12.0206. doi: 10.2460/ajvr.21.12.0206.
To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses.
6 healthy geldings.
A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms. Prior to endotoxin challenge (lipopolysaccharide, 30 ng/kg IV over 30 minutes), horses received misoprostol (5 µg/kg once) per os (M-PO) or per rectum (M-PR) or water as control (CON). Clinical parameters were evaluated and blood samples obtained to measure plasma misoprostol free acid concentration, leukocyte counts, and tumor necrosis factor-α (TNFα) and interleukin 6 (IL-6) leukocyte gene expression and serum concentrations.
In the M-PO treatment arm, maximum plasma concentration and area under the concentration-versus-time curve (mean ± SD) were higher (5,209 ± 3,487 pg/mL and 17,998,254 ± 13,194,420 h·pg/mL, respectively) and median (interquartile range) time to maximum concentration (25 min [18 to 34 min]) was longer than in the M-PR treatment arm (854 ± 855 pg/mL; 644,960 ± 558,866 h·pg/mL; 3 min [3 to 3.5 min]). Significant differences in clinical parameters, leukocyte counts, and TNFα or IL-6 gene expression or serum protein concentration were not detected. Downregulation of relative gene expression was appreciated for individual horses in the M-PO and M-PR treatment arms at select time points.
Considerable variability in measured parameters was detected among horses within and between treatment arms. Misoprostol absorption and systemic exposure after PO administration differed from previous reports in horses not administered LPS. Investigation of multidose administration of misoprostol is warranted to better evaluate efficacy as an anti-inflammatory therapeutic.
描述在脂多糖（内毒素）挑战的马匹中，经口或直肠给予米索前列醇后的药代动力学和抗炎效果。
6 匹健康去势公马。
采用随机 3 处理交叉设计，每个治疗臂之间的最小洗脱期为 28 天。在进行内毒素挑战（静脉内给予 30ng/kg 脂多糖 30 分钟）之前，马匹经口（M-PO）或直肠（M-PR）给予米索前列醇（5μg/kg 一次）或水作为对照（CON）。评估临床参数并采集血液样本以测量血浆米索前列醇游离酸浓度、白细胞计数以及肿瘤坏死因子-α（TNFα）和白细胞介素 6（IL-6）白细胞基因表达和血清浓度。
在 M-PO 治疗臂中，最大血浆浓度和浓度-时间曲线下面积（平均值±SD）更高（分别为 5209±3487pg/ml 和 17998254±13194420h·pg/ml），中位（四分位间距）达峰时间（25 分钟[18 至 34 分钟]）长于 M-PR 治疗臂（854±855pg/ml；644960±558866h·pg/ml；3 分钟[3 至 3.5 分钟]）。在临床参数、白细胞计数、TNFα或 IL-6 基因表达或血清蛋白浓度方面未检测到显著差异。在 M-PO 和 M-PR 治疗臂的特定时间点，个别马匹的相对基因表达出现下调。
在治疗臂内和臂间的马匹中，测量的参数存在相当大的变异性。经口给予米索前列醇后的吸收和全身暴露与未给予 LPS 的马匹的先前报道不同。有必要研究米索前列醇的多次给药，以更好地评估其作为抗炎治疗的疗效。
