Department of Clinical Pharmacy, Bicetre Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
Liver Transpl. 2011 Oct;17(10):1152-8. doi: 10.1002/lt.22364.
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.
霉酚酸酯（MMF）目前常用于儿科肝移植受者，但尚未针对该人群制定明确的剂量方案。本研究旨在确定儿科肝移植受者所需的 MMF 剂量，以使霉酚酸（MPA）的血药浓度-时间曲线下面积（AUC）0 至 12 小时（AUC（0-12））大于 30mg·h/L。在肝移植后中位数为 11.0 个月（范围 0.5-88.0 个月）时，对 15 例儿童（中位数年龄=8.3 岁，范围 1.1-15.2 岁）进行了一项药代动力学研究。MMF 初始剂量中位数为 300mg/m2 ，每日 2 次（范围为 186-554mg/m2 ，每日 2 次）。15 例患者中有 13 例 MPA AUC（0-12）值小于 30mg·h/L。除 1 例外，所有患者均需增加 MMF 剂量。达到定义的目标 30mg·h/L 以上的 MPA AUC（0-12）值所需的 MMF 剂量范围为 371 至 1014mg/m2 /天。对于同时接受 MMF 和利福平治疗的 2 例患者，尽管 MMF 剂量增加了 2 倍，但 MPA AUC（0-12）值仍较低。总之，初始 MMF 剂量为 600mg/m2 ，每日 2 次，除同时给予利福平外，MPA AUC（0-12）值大于 30mg·h/L 阈值。由于 MPA 药代动力学的个体间变异性很大，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 与利福平合用。
