The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2024-02-09 DOI:10.1111/jvp.13430
Kaitlyn Bello, Gwendolen Lorch, Mark G. Papich, Kyeongmin Kim, Ramiro E. Toribio, Liwei Yan, Zhiliang Xie, Kasey Hill, Mitch A. Phelps
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Abstract

Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six-day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p = .038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single-dose administration but may be significant in horses receiving long-term MMF treatment.

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食物对健康马匹体内霉酚酸酯药代动力学的影响。
马匹免疫介导疾病的治疗需要额外的免疫调节治疗。霉酚酸酯(MMF)是一种免疫调节药物,在人类和兽医中用于预防移植物排斥反应和治疗自身免疫性疾病。很少有研究调查 MMF 在马匹体内的药代动力学。本研究旨在评估健康马匹在进食与禁食状态下单剂 MMF 的药代动力学。六匹健康的标准马母马分别在进食和禁食状态下通过鼻胃(NG)管给药 MMF 10 mg/kg。两次给药之间有六天的缓冲期。除 8 小时外,其他时间点的霉酚酸 (MPA) 浓度均无统计学差异,空腹状态下的血浆代谢物浓度明显高于进食状态(p = .038)。只有在空腹状态下才能看到肠肝再循环的证据;这在单剂量给药的马匹中不会产生临床差异,但在长期接受 MMF 治疗的马匹中可能很重要。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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