Optimization of the Dosing Regimen of Mycophenolate Mofetil in Pediatric Liver Transplant Recipients
Optimization of the Dosing Regimen of Mycophenolate Mofetil in Pediatric Liver Transplant Recipients
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DOI：
10.1002/lt.22364
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发表时间：
2011-10-01
影响因子：
4.6
通讯作者：
Furlan, Valerie
中科院分区：
文献类型：
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作者：
Barau, Caroline;Barrail-Tran, Aurelie;Furlan, Valerie
吗替麦考酚酯 (MMF) 目前常用于儿科肝移植受者，但尚未针对该人群提出明确的给药方案建议。本研究的目的是确定儿科肝移植受者在霉酚酸 (MPA) 大于 30 mg/h 时达到 0 至 12 小时血浆浓度-时间曲线下面积 (AUC(0-12)) 所需的 MMF 剂量。肝移植后平均 11.0 个月（范围 0.5-88.0 个月）对 15 名儿童（中位年龄 8.3 岁，范围 1.1-15.2 岁）进行了药代动力学研究。 MMF 最初以中位起始剂量 300 mg/m(2) 每天两次（范围 186-554 mg/m(2) 每天两次）引入。 15 名患者中有 13 名的 MPA AUC(0-12) 值低于 30 mg·小时/L。除 1 例外，所有患者的 MMF 剂量都必须增加。达到大于 30 mg/h/L 定义目标的 MPA AUC(0-12) 值所需的 MMF 剂量范围为 371 至 1014 mg/m(2)/天。对于 2 名除 MMF 之外还接受利福平的患者，尽管 MMF 剂量增加了 2 倍，MPA AUC(0-12) 值仍然较低。总之，每天两次 600 mg/m(2) 的初始 MMF 剂量导致 MPA AUC(0-12) 值大于 30 mg/h/L 阈值，除非同时服用利福平。由于 MPA 药代动力学存在重要的个体差异，建议进行治疗药物监测以优化每日 MMF 剂量。此外，这些结果表明应避免 MPA 与利福平同时给药。肝脏移植 17：1152-1158，2011。(C) 2011 AASLD。
Mycophenolate mofetil (MMF) is now commonly used in pediatric liver transplant recipients, but no clear recommendations about the dosing regimen have been made for this population. The aim of this study was to determine the MMF dosage required for pediatric liver transplant recipients to achieve an area under the plasma concentration-time curve from 0 to 12 hours (AUC(0-12)) for mycophenolic acid (MPA) greater than 30 mg hour/L. A pharmacokinetic study of 15 children (median age 8.3 years, range 1.1-15.2 years) was performed at a median of 11.0 months (range 0.5-88.0 months) after liver transplantation. MMF was initially introduced at a median starting dose of 300 mg/m(2) twice a day (range 186-554 mg/m(2) twice a day). Thirteen of the 15 patients had an MPA AUC(0-12) value less than 30 mg hour/L. The MMF dosage had to be increased in all patients except 1. The MMF dosage required to reach an MPA AUC(0-12) value greater than the defined target of 30 mg hour/L ranged from 371 to 1014 mg/m(2)/day. For 2 patients who received rifampin in addition to MMF, the MPA AUC(0-12) value remained low despite a 2-fold increase in the MMF dosage. In conclusion, an initial MMF dose of 600 mg/m(2) twice a day led to MPA AUC(0-12) values greater than the 30 mg hour/L threshold except when rifampin was coadministered. Because of the important interindividual variability of MPA pharmacokinetics, therapeutic drug monitoring is recommended for optimizing the daily MMF dosage. Furthermore, these results suggest that the coadministration of MPA with rifampin should be avoided. Liver Transpl 17: 1152-1158, 2011. (C) 2011 AASLD.