Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington.
J Vet Intern Med. 2019 Sep;33(5):2020-2028. doi: 10.1111/jvim.15585. Epub 2019 Aug 19.
Mycophenolate mofetil (MMF) is an immunosuppressant used in human and veterinary medicine. Little pharmacokinetic and pharmacodynamic information on MMF is available in cats.
To evaluate the plasma disposition of mycophenolic acid (MPA) and assess its effect on total peripheral blood mononuclear cells and CD4 /CD8 ratios after PO administration of MMF.
Healthy cats (n = 10).
Mycophenolate mofetil was administered at a dosage of 10 mg/kg q12h (n = 3), 15 mg/kg q12h (n = 3), and 15 mg/kg q8h (n = 4) for 7 days. Concentrations of MPA and derivatives were determined using ultra-high-performance liquid chromatography. Flow cytometry was used to assess CD4 /CD8 T-cell ratios.
All cats biotransformed MMF into MPA. Half of the cats (5/10) had adverse effects within 1 week of MMF administration. Area under the curve limit of quantification (AUC ) of MPA ranged from 1.27 to 2.03 hours·μg/mL and from 1.77 to 8.54 hours·μg/mL after the first and last PO dose of 10 mg/kg. The AUC of MPA ranged from 2.18 to 31 hours·μg/mL after the first dose of 15 mg/kg of MMF. Before the first dose of MMF, the average total number of PBMC ranged from 1.2 to 9.3 million/mL. At the last dose of MMF, the average total number of PBMC ranged from 3 to 5 million/mL.
Mycophenolic acid was detected in all cats. The dose 10 mg/kg given q12h for 1 week was tolerated (n = 3). The efficacy of MMF as an immunosuppressant and long-term safety in cats of this dosage regimen is unknown.
霉酚酸酯（MMF）是一种在人和兽医医学中使用的免疫抑制剂。在猫中，关于 MMF 的药代动力学和药效学信息很少。
评估霉酚酸（MPA）在猫体内的血浆分布情况，并评估其在 PO 给予 MMF 后对总外周血单核细胞和 CD4/CD8 比值的影响。
健康猫（n=10）。
MMF 以 10mg/kg q12h（n=3）、15mg/kg q12h（n=3）和 15mg/kg q8h（n=4）的剂量 PO 给药 7 天。使用超高效液相色谱法测定 MPA 及其衍生物的浓度。使用流式细胞术评估 CD4/CD8 T 细胞比值。
所有猫均将 MMF 生物转化为 MPA。在 MMF 给药后 1 周内，有一半（5/10）的猫出现不良反应。MPA 的 AUC 下限定量（AUC）范围在第一次和最后一次 PO 剂量 10mg/kg 时分别为 1.27 至 2.03 小时·μg/mL 和 1.77 至 8.54 小时·μg/mL。在第一次给予 15mg/kg MMF 时，MPA 的 AUC 范围为 2.18 至 31 小时·μg/mL。在 MMF 的第一次剂量之前，平均总 PBMC 数范围为 1.2 至 9.3 百万/mL。在 MMF 的最后一剂时，平均总 PBMC 数范围为 3 至 5 百万/mL。
所有猫均检测到 MPA。在 1 周内以 10mg/kg q12h 的剂量给药时可耐受（n=3）。在这种剂量方案下，MMF 作为免疫抑制剂的疗效和长期安全性在猫中尚不清楚。
