肾移植受者霉酚酸浓度的监测

Monitoring of mycophenolic acid concentration in kidney transplant recipients

本文总结了近十年来霉酚酸(MPA)血药浓度监测在肾移植受者中应用的研究进展,为进一步合理使用MPA类药物、探究如何优化我国人群抗排斥方案提供线索。MPA可通过吗替麦考酚酯(MMF)或霉酚酸钠肠溶片(EC-MPS)经胃肠道吸收代谢转化而得,主要代谢物为7-O-葡萄糖苷酸霉酚酸(MPAG)。人群药代动力学研究表明MPA代谢存在显著的个体间差异及时间相关的个体内差异,影响因素主要包括种族、人群、移植肾功能、血浆白蛋白水平、联合钙调神经蛋白抑制剂(CNIs)类药物种类等。MPA明确的浓度-效应关系及显著的个体间和个体内药代学差异为MPA血药浓度监测提供了充分的依据。MPA血浆浓度检测方法主要有高效液相色谱法和酶免疫分析法。对于需要进行血药浓度监测的免疫抑制药物,服用剂量并不是预测其暴露水平的可行指标,而MPAAUC0～12h是观察其全身暴露水平、进行血药浓度监测的金标准,目前认为对于肾移植受者MPA-AUC0～12h的目标范围应控制在30～60 mg·h/L。MPA-AUC0～12h过低会增加患者发生急性排斥反应的风险,而MPA-AUC0～12h过高并不增加患者受益的机会,但是与药物毒性无明显的相关性。尽管对MPA血药浓度监测是否使患者受益仍然没有定论,但确实对于指导临床MPA合理化用药带来积极意义。

Mycophenolic Acid （MPA） is a metabolite derived from gastro-intestinal absorption of mycophenolate mofetil （MMF） or enteric-coated mycophenolate sodium （EC-MPS） and transforms into MPAG. Pharmaeokinetic studies in mass have shown significant inter-patient variability and a time-dependent intra-patient change. It could be influenced by many factors including race, humanity, donor kidney function, serum albumin level, and combined calcineurin inhibitors types. The concentration-effect relationship and significant variability seen in pharmacokinetics of MPA in both inter-and intra-individual are sufficient evidences for MPA therapeutic drug monitoring. The plasma concentration of MPA can be examined in two different methods via high-performance liquid chromatography （HPLC） and enzyme immunoassay （EIA）. For therapeutic drug monitoring of immunosuppressive drugs,its dosage does not feasibly predict the exposure value. MPA- AUC0-12h is observed for its exposure value and is the golden standard for therapeutic drug monitoring. The target range control exposure of MPA-AUC0-12h in the kidney transplant recipients is generally considered between 30 mg.h/L to 60 mg.h/L. Under its lower concentration increases the risk of acute rejection, while above the upper concentration has no apparent additional benefit, but neither drug toxicity associated. Although it is still not conclusive about whether MPA therapeutic drug monitoring is beneficial for patients, but it indeed has brought significant importance for conducting clinical rational drug use of MMF. Summarizing the research progress about therapeutic drug monitoring of mycophenolic acid （MPA） in kidney transplant recipients since last decade,this review underlines the further rational use of MPA and hence explores clues in advanced anti-rejection therapy.