The neurokinin-1 (NK-1) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood in horses, and clinical use of NK-1 receptor antagonists has not been reported. This study aimed to determine the pharmacokinetics and safety of maropitant after administration of multiple doses. We hypothesized that maropitant concentrations would be similar at steady state to those reported in dogs, with minimal adverse effects. Maropitant was administered at 4 mg/kg orally, once daily for 5 days in seven adult horses. Serial plasma maropitant concentrations were measured by liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic parameters were determined. The maximum, minimum, and average concentrations of maropitant achieved at steady state were 375.5 ± 200, 16.8 ± 7.7, and 73.5 ± 45.1 ng/ml, respectively. The terminal elimination half-life was 11.6 ± 1.4 hr, and the accumulation index was 1.3 ± 0.07. Heart rate decreased between Day 1 and Day 5 (p = .005), with three horses having heart rates of 20 beats per minute and atrioventricular block on Day 5. Pharmacokinetics of repeated maropitant administration suggests the drug could be considered for use in healthy horses. Further investigation on the clinical relevancy of its cardiac effects is warranted.

中文翻译：

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口服给予多剂量成年马后柠檬酸马洛匹坦的药代动力学。

神经激肽-1（NK-1）受体拮抗剂柠檬酸马洛匹坦，可减轻狗和猫的恶心和呕吐。恶心在马中了解甚少，尚未报道NK-1受体拮抗剂的临床用途。这项研究旨在确定多次给药后马洛匹坦的药代动力学和安全性。我们假设稳定状态下的maropitant浓度与狗中报道的浓度相似，且不良反应最小。七只成年马口服Maropitant的剂量为4 mg / kg，每天一次，持续5天。通过液相色谱-质谱法测定血浆血浆木聚糖含量。确定了非房室药代动力学参数。稳定状态下所含maropitant的最大，最小和平均浓度分别为375.5±200、16.8±7.7和73.5±45。分别为1 ng / ml。末端消除半衰期为11.6±1.4小时，累积指数为1.3±0.07。第1天到第5天之间的心率下降（p = 0.005），三匹马的心率每分钟20次，第5天出现房室传导阻滞。反复服用木偶蛋白的药代动力学表明该药物可考虑用于健康的马。有必要对其心脏效应的临床相关性进行进一步研究。反复服用maropitant的药代动力学表明，该药物可考虑用于健康马匹。有必要对其心脏效应的临床相关性进行进一步研究。反复服用maropitant的药代动力学表明，该药物可考虑用于健康马匹。有必要对其心脏效应的临床相关性进行进一步研究。