Laboratoire de Pharmacologie-toxicologie, Service de Pharmacie, GH Cochin-Saint Vincent-de-Paul, 75014 Paris, France.
J Clin Pharmacol. 2010 Oct;50(10):1202-10. doi: 10.1177/0091270009358084. Epub 2010 Feb 9.
Mycophenolate mofetil (MMF) pharmacokinetics variability in liver transplant recipients during the early posttransplantation period may be related to changes in mycophenolic acid (MPA) protein binding. This study aimed at characterizing the variation of free MPA exposure with respect to time since transplantation. Three groups (A, B, C) were compared. The median posttransplantation time was 12 days (A, n = 26 pharmacokinetic sessions), 36 days (B, n = 25), and 867 days (C, n = 21). The median MPA AUC(0-12) in group A (26.8 mg x h/L) was significantly lower than in groups B (45.2 mg x h/L, P = .031) and C (43.5 mg x h/L, P = .004). Free MPA AUC(0-12) was comparable whatever the time (0.41, 0.34, and 0.33 mg x h/L, respectively). MPA apparent clearance (CL/F) was significantly correlated with MPA free fraction (r = 0.60, P < .0001) and approximately 1.7-fold higher in group A compared to groups B and C (P < .05). Enhanced CL/F in relation with an increase in MPA free fraction results in a low AUC of total MPA during the first postoperative month, but on average, at the population level, the exposure to free MPA is not altered, suggesting that total MPA AUC should not be used to adapt MMF dosing during this period.
在肝移植受者移植后早期，霉酚酸（MPA）蛋白结合的变化可能与麦考酚酸（MMF）药代动力学变异性有关。本研究旨在研究游离 MPA 暴露随移植后时间的变化特征。比较了三组（A、B、C）。移植后时间中位数分别为 12 天（A，n=26 个药代动力学期）、36 天（B，n=25）和 867 天（C，n=21）。A 组（26.8 mg×h/L）MPA AUC（0-12）中位数明显低于 B 组（45.2 mg×h/L，P=0.031）和 C 组（43.5 mg×h/L，P=0.004）。无论时间如何，游离 MPA AUC（0-12）均相似（分别为 0.41、0.34 和 0.33 mg×h/L）。MPA 表观清除率（CL/F）与 MPA 游离分数显著相关（r=0.60，P<0.0001），A 组与 B 组和 C 组相比，CL/F 增加约 1.7 倍（P<0.05）。与 MPA 游离分数增加相关的增强 CL/F 导致术后第一个月总 MPA 的 AUC 较低，但平均而言，在人群水平上，游离 MPA 的暴露未改变，表明在此期间不应使用总 MPA AUC 来调整 MMF 剂量。
