血霉酚酸水平监测在肾移植临床的应用现状及进展

Therapeutic drug monitoring of mycophenolic acid in renal transplantation

本综述通过总结近几年霉酚酸(MPA)水平监测的研究进展,为进一步合理使用MPA并探究如何优化国人抗排斥方案提供线索。MPA检测方法分为高效液相色谱法(HPLC)和酶免疫分析法(EIA),其中HPLC联用紫外检测器、荧光检测器或串联质谱,和EMIT可测定MPA总浓度和游离浓度。MPA可通过MMF或EC-MPS经胃肠道吸收代谢转化而得,主要代谢物为MPAG。MPA的代谢存在明显的个体内和个体间差异,影响因素主要包括种族,血浆白蛋白浓度,移植肾功能,进食和药物配伍。低MPA AUC或谷浓度值会增加急性排斥的风险,高MPA AUC或谷浓度值会增加发生不良反应的风险,一般认为监测时应控制MPA AUC0-12在30～60 mg/(h.L)。血游离MPA暴露量的监测可能对预测发生不良反应的风险更有意义。尽管对治疗药物监测是否使患者受益仍然没有定论,但监测确实对临床调整MPA用药带来积极意义。

This review aims to summarize the latest researches on therapeutic drug monitoring of mycophenolic acid,forming the basis for the proper prescription of Mycophenolic Acid（MPA） and the optimization of anti-rejection medication for Chinese.The technology of measuring the total and free MPA concentration in the plasma includes high-performance liquid chromatography with ultraviolet detector,fluorescence detector and tandem mass spectrometer respectively,and enzyme-multiplied immunoassay technique.Either MMF or EC-MPS can be absorbed by the gastrointestinal tract and metabolized into MPA,whose main metabolite is MPAG.MPA displays large between-and within-subject pharmacokinetic variability.The pharmacokinetics of MPA is mainly interfered with by race,plasmic albumin concentration,the renal function,food,and interactions with other immunosuppressant drug.Low MPA AUC or trough concentration may increase the risk of acute rejection,while the high ones may cause more adverse effects.In TDM,MPA AUC should be maintained between 30 and 60 mg·h·L-1.The monitoring of free MPA may provide greater predictive value in terms of adverse effects.TDM actually helps the clinicians to adjust the MPA dose more appropriately,although it is still controversial whether TDM benefits the patients or not.