Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
J Vet Intern Med. 2023 Sep-Oct;37(5):1907-1916. doi: 10.1111/jvim.16797. Epub 2023 Jul 19.
Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses.
HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen.
Six healthy Standardbred mares.
Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability.
Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC ) of 12 594 h × ng/mL (8567-19 488 h × ng/mL) and terminal half-life (T ) of 11.3 hours (7.5-15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment.
Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.
需要额外有效的免疫调节治疗来治疗马的免疫介导性疾病。霉酚酸酯（MMF）是一种免疫抑制剂，值得评估作为马的可行治疗药物。
假设/目的：评估健康马口服 MMF 多日给药的药代动力学（PK），并确定该给药方案的耐受性。
六匹健康的标准bred 母马。
马在进食状态下每天口服 MMF 10mg/kg，q12h，共 7 天。在第 1 天和第 7 天的 12 小时内进行连续采样，并在每天早上给药前每 24 小时采集一次谷值样本。进行非房室 PK 分析以确定主要 PK 参数，然后计算几何平均值和变异系数。全血细胞计数（CBC）、血清生化谱、体格检查和粪便评分用于评估剂量耐受性。
7 天的治疗导致马的麦考酚酸（MPA）曲线下面积（AUC）为 12594h×ng/mL（8567-19488h×ng/mL）和终末半衰期（T）为 11.3 小时（7.5-15.9 小时），所有接受治疗的马均出现轻微的代谢物蓄积。第 7 天，2 匹马的粪便中检测到沙门氏菌，所有马在治疗的第 7 天均出现骨髓抑制、高胆红素血症、食欲不振、胃肠道蠕动减少和粪便排出减少。
在治疗的第 1 周内，MMF 按 10mg/kg PO q12h 给药导致血液学和临床毒性。需要减少 MMF 的剂量、频率或两者兼而有之，以避免出现腹痛。药物监测应包括频繁的血象、血清生化谱和严格的生物安全方案。
