Tedesco-Silva H, Bastien M-C, Choi L, Felipe C, Campestrini J, Picard F, Schmouder R
Hospital do Rim e Hipertensao, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
Transplant Proc. 2005 Mar;37(2):852-5. doi: 10.1016/j.transproceed.2004.12.186.
Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is an effective immunosuppressive treatment in renal transplant recipients but is known to have gastrointestinal side effects. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) is a new formulation for delivering MPA. This open-label, two-period, cross-over study was carried out to characterize the time course of MPA and its metabolites, mycophenolic acid glucuronide (MPAG) and acyl mycophenolic acid glucuronide (AcMPAG) in stable renal transplant patients (n = 40) after 28-day chronic dosing with EC-MPS (720 mg bid) or MMF (1000 mg bid). The relative abundance and exposure of all three compounds was also assessed. EC-MPS demonstrated the typical pharmacokinetic profile of an enteric-coated formulation with a delayed release of MPA compared with MMF (Tmax 2.5 versus 1.0 hours, respectively). Consistent with a similar disposition of MPA, both EC-MPS and MMF treatments resulted in the same ratio of MPAG to MPA exposure, 23:1. Furthermore, comparison of the AUC of MPAG and AcMPAG for both treatments indicated that steady state MPAG exposure was 75 to 90 times that of AcMPAG, confirming MPAG as the predominant metabolite of MPA. AcMPAG has been identified as a possible active metabolite of MPA; the present study indicates that AcMPAG may contribute around 14% of the exposure to active drug after administration of MPA. Both EC-MPS and MMF treatments were well tolerated over the 1-month period of chronic treatment. In summary, consistent with its enteric-coated design, EC-MPS delays delivery of MPA, but results in similar exposure to that provided by MMF.
霉酚酸酯（MMF）是霉酚酸（MPA）的前体药物，是肾移植受者有效的免疫抑制治疗药物，但已知有胃肠道副作用。肠溶包衣的霉酚酸钠（EC-MPS；米芙）是一种用于递送MPA的新制剂。本开放标签、两期、交叉研究旨在描述稳定肾移植患者（n = 40）在接受28天EC-MPS（720 mg，每日两次）或MMF（1000 mg，每日两次）慢性给药后MPA及其代谢产物霉酚酸葡糖苷酸（MPAG）和酰基霉酚酸葡糖苷酸（AcMPAG）的时间过程。还评估了所有三种化合物的相对丰度和暴露情况。与MMF相比，EC-MPS显示出肠溶包衣制剂典型的药代动力学特征，MPA释放延迟（Tmax分别为2.5小时和1.0小时）。与MPA的相似处置一致，EC-MPS和MMF治疗导致MPAG与MPA暴露的比例相同，为23:1。此外，两种治疗的MPAG和AcMPAG的AUC比较表明，稳态MPAG暴露是AcMPAG的75至90倍，证实MPAG是MPA的主要代谢产物。AcMPAG已被确定为MPA可能的活性代谢产物；本研究表明，给药MPA后，AcMPAG可能贡献约14%的活性药物暴露。在1个月的慢性治疗期间，EC-MPS和MMF治疗均耐受性良好。总之，与肠溶包衣设计一致，EC-MPS延迟了MPA的递送，但导致的暴露与MMF提供的相似。
