Pharmacokinetics of mycophenolate sodium and comparison with the mofetil transplant recipients formulation in stable kidney
Pharmacokinetics of mycophenolate sodium and comparison with the mofetil transplant recipients formulation in stable kidney
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DOI：
10.2215/cjn.02820707
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发表时间：
2007-11-01
影响因子：
9.8
通讯作者：
Perico, Norberto
中科院分区：
文献类型：
--
作者：
Cattaneo, Dario;Cortinovis, Monica;Perico, Norberto
背景和目标：霉酚酸酯的引入改善了器官移植后的移植物存活率，然而，其使用可能受到重要不良反应的限制。为了克服这些问题，麦考酚酸钠的肠溶包衣制剂已被开发，但从这个配方释放的麦考酚酸的药代动力学数据是scanty.Design，设置，参与者，和测量：在32名肾移植受者谁被给予的肠溶包衣制剂的麦考酚酸钠（n = 12）或麦考酚酸吗替酯（n = 20）进行了药代动力学研究。比较移植后6、12、18和24个月时两种制剂的麦考酚酸谱。随后，所有接受肠溶包衣制剂的患者被转移到吗替麦考酚酸酯，药代动力学评价repeated.Results：在术后6个月，异常和可变的药代动力学曲线被发现在患者谁被给予肠溶包衣制剂，而那些谁服用吗替麦考酚酸酯有规律的霉酚酸动力学曲线。与接受吗替麦考酚酯的患者相比，接受肠溶制剂的患者的麦考酚酸达到最大药物浓度的时间范围为0 - 480 min，剂量调整后的麦考酚酸谷浓度更高。从麦考酚钠肠溶制剂转换为麦考酚酸吗替酯导致麦考酚酸动力学特征的改善。结论：鉴于麦考酚酸监测在移植环境中出现的临床益处，应考虑麦考酚钠肠溶制剂的治疗药物监测问题。
Background and objectives: The introduction of mycophenolate mofetil has improved graft survival after organ transplantation; however, its use may be limited by important adverse effects. For overcoming these problems, an enteric-coated formulation of mycophenolate sodium has been developed, but pharmacokinetic data of mycophenolic acid release from this formulation are scanty.Design, setting, participants, & measurements: Pharmacokinetic studies in 32 kidney transplant recipients who were given the enteric-coated formulation of mycophenolate sodium (n = 12) or mycophenolate mofetil (n = 20) were performed. The profiles of mycophenolic acid from the two formulations at months 6, 12, 18, and 24 after transplantation were compared. Subsequently, all patients who were receiving the enteric-coated formulation were shifted to mycophenolate mofetil, and the pharmacokinetic evaluations were repeated.Results: At month 6 after surgery, aberrant and variable pharmacokinetic curves were found in patients who were given the enteric-coated formulation, whereas those who were taking mycophenolate mofetil had regular mycophenolic acid kinetic profiles. Patients who were taking the enteric-coated formulation had mycophenolic acid time of occurrence for maximum drug concentration that ranged from 0 to 480 min. and higher dosage-adjusted mycophenolic acid trough levels compared with patients who were given mycophenolate mofetil. Conversion from the enteric-coated formulation of mycophenolate sodium to mycophenolate mofetil resulted in an improvement of the mycophenolic acid kinetics profiles.Conclusions: Given the emerging clinical benefit of mycophenolic acid monitoring in the transplant setting, therapeutic drug monitoring problems with the enteric-coated formulation of mycophenolate sodium should be taken into account.