心脏移植后吗替麦考酚酯的个体化应用

Individualized mycophenolate mofetil therapy based on monitoring of mycophenolic acid trough level in cardiac transplant recipients

目的比较心脏移植术后吗替麦考酚酯（MMF）个体化给药方案与固定给药方案的临床疗效，总结基于血霉酚酸（MPA）浓度监测的MMF个体化方案应用经验。方法研究组48例受者为2010年1月至2011年12月间接受心脏移植术，术后依据临床事件及血MPA浓度谷值（MPA-G）进行个体化MMF剂量调整，MPA-Co目标浓度为2．0～4．0mg／L，随访12个月；对照组从数据库中选取2007年1月至2009年12月行心脏移植手术，并且与研究组配对同质程度较高的55例受者，术后服用固定剂量MMF，如有不良事件发生则经验性调整剂量，回顾术后12个月内的随访数据。记录并比较二组间服药量、急性排斥反应发生率及MMF相关不良反应发生率。结果研究组术后12个月随访率95．8%，MMF用药1周后首次检测MPA-AUG0-12为（54．37±17．03）mg·h·L-1，MPA-C10为（3．44±0．58）mg／L，明显高于术后12个月时的（2．79±0．54）mg／L（P〈0．05）。术后1个月时研究组MMF用量为（1．49±0．48）g／d，明显低于对照组的（1．96±0．39）g／d（P〈0．05）；术后12个月时MMF用量分别为（1．61±0．77）g／d和（1．68±0．84）g／d（P〉0．05）。研究组及对照组急性排斥反应发生率分别为8．7％和9．1％（P〉0．05）。研究组MMF相关不良反应总体发生率为47．8％，明显低于对照组的67．3％（P〈0．05），其中有57．6％的不良反应发生在术后1个月以内。结论与固定剂量给药方案相比，MPA-Co监测下的MMF个体化治疗最大优势在于可以在不良事件发生前对药量进行主动调整，从而在很大程度上起到了减少MMF相关不良反应的作用，进一步提高了心脏移植疗效。

Objective To compare clinical outcomes in cardiac transplant recipients treated with individualized dosing （ID） and fixed dosing （FD） of mycophenolate mofetil （MMF）. Methods Fortyeight de novo cardiac transplant patients in ID group received MMF （2. 0 g/day） in combination with calcineurin inhibitors and prednisone. The MMF dosages were adjusted individually based on clinical events and MPA trough levels （MPA-CO）. The target range of Co was maintained within 2. 0-4. 0 mg/L. The FD group included 55 recipients retrospectively from the transplant database who were also treated with MMF （2. 0 g/day）. In this group, the MMF dose adjustment was performed empirically according to clinical events only. All of the follow-up data were collected up to 12 months post-transplantation. Results The follow-up rate was 95.8% and the mean MPA-AUCO 12 was （54. 37 ± 17. 03） mg h1 L1 in the ID group. The mean MPA-CO on the day 7 post-transplantation was significantly higher in the ID group than that at 12th month [（3.44 ± 0. 58） mg/L vs. （2. 79 ± 0. 54） mg/L] （P〈0. 05）. The dose of MMF was significantly lower in the ID group at 4th week posttransplantation than in control group [（1.49 ± 0. 48） g/day vs. （1.96 ± 0. 39） g/d] （P〈0. 05）, while there was no significant difference at 12 th month post-transplantation [（1.61 ± 0. 77） g/day vs. （1.68 ± 0. 84） g/day] （P〉0. 05）. No significant difference was found in the incidence of acute rejection episode between two groups （8. 7% vs. 9. 1%, P〉0. 05）. 57. 6% of overall side effects were observed within one month postoperatively, and the incidence of MPA-related side effects was significantly lower in the ID group than in the control group （47. 8% vs. 67. 3%, P〈 0. 05）.Conclusion It was demonstrated that individualized use of MMF based on therapeutic drug monitoring may prevent MMF-related side effect and appears to be valuable to optimize the treatment of cardiac transplantation.