Berger Iona, Haubrich Kathryn, Ensom Mary H H, Carr Roxane
Lower Mainland Pharmacy Services, Children's & Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Pediatr Transplant. 2019 Mar;23(2):e13355. doi: 10.1111/petr.13355. Epub 2019 Jan 28.
MMF, a prodrug converted to the active form MPA, is an immunosuppressant used to prevent rejection in solid organ transplant recipients. MPA exposure, defined by AUC, can be estimated using limited sampling strategies (LSS). The relationship between MPA AUC and clinical outcomes has not been studied in pediatrics. The objectives were to describe the relationship of MPA AUC (estimated via LSS) with adverse effects and rates of rejection, and to compare clinical outcomes between different MPA monitoring practices. Descriptive statistics were used to summarize demographics, adverse effects, and rejection. Thirty-three patients (91 trough concentrations and 12 LSS sets) aged 2-20 years old were included. The estimated median MPA AUCs (David-Neto and Filler) were higher for those who did not have any adverse effects reported (65.85 and 85.05 mgh/L, respectively) compared to those who had an adverse effect (60.75 and 54.2 mgh/L, respectively). The median trough concentration when no adverse effects occurred was comparable to when adverse effects occurred. The median MPA AUC at which rejection occurred was lower than in those without rejection. The median trough concentration at which rejection occurred was higher than those without rejection (3.1 mg/L compared to 1.9 mg/L). The occurrence of adverse effects or rejection was not shown to be related to measured MPA trough or AUC outside of the target therapeutic range. The value of MPA concentration monitoring remains unclear; therefore, the practice of monitoring MPA AUC by LSS or trough concentrations should be reconsidered.
霉酚酸酯（MMF）是一种前体药物，可转化为活性形式的霉酚酸（MPA），是一种免疫抑制剂，用于预防实体器官移植受者的排斥反应。通过曲线下面积（AUC）定义的MPA暴露量可使用有限采样策略（LSS）进行估算。MPA AUC与临床结局之间的关系尚未在儿科中进行研究。目的是描述MPA AUC（通过LSS估算）与不良反应和排斥率之间的关系，并比较不同MPA监测方法之间的临床结局。使用描述性统计来总结人口统计学、不良反应和排斥情况。纳入了33例年龄在2至20岁之间的患者（91个谷浓度和12组LSS）。与报告有不良反应的患者相比，未报告有任何不良反应的患者的估计MPA AUC中位数（David-Neto法和Filler法）更高（分别为65.85和85.05mg·h/L）（分别为60.75和54.2mg·h/L）。未发生不良反应时的谷浓度中位数与发生不良反应时相当。发生排斥时的MPA AUC中位数低于未发生排斥的患者。发生排斥时的谷浓度中位数高于未发生排斥的患者（分别为3.1mg/L和1.9mg/L）。未显示不良反应或排斥的发生与目标治疗范围之外测得的MPA谷浓度或AUC相关。MPA浓度监测的价值仍不明确；因此，应重新考虑通过LSS或谷浓度监测MPA AUC的做法。
