环孢素A的药物基因组学与个体化用药的研究现状及进展

Research current situation and progress on pharmacogenomics and personalized medicine of cyclosporine A

环孢素(CsA)作为一种新型强效免疫抑制剂,近年来广泛应用于器官移植术后的抗排斥反应治疗。由于其治疗指数狭窄,个体间差异大,如何在临床合理使用CsA一直是广大学者关注的热点。CsA的生物利用度和代谢主要受药物代谢酶CYP3A和转运蛋白P-糖蛋白(P-gp)的影响,而不同个体间CYP3A与多药耐药基因(MDR1)基因多态性则是CYP3A酶和P-gp产生活性差异的分子机制。此外,合并用药、饮食结构等非遗传因素也是影响CsA疗效的重要原因,本文就近年来CsA药物基因组学研究进展结合非遗传因素予以综述,为临床个体化用药提供参考,确保患者安全合理用药。

Cyclosporine （CsA）, as a hOVer potent immunosuppressant, is widely used in or- gan transplantation in recent years. Due to its narrow therapeutic index and individual differ- ence, it has been greatly concerned that how CsA can be used rationally in clinic. The bio- availability and metabolic of CsA are mainly af- fected by drug-metabolizing enzymes CYP3A and P-glycoprotein transporter protein （P-gp）, while the individual differences of gene polymor- phism of CYP3A and multi-drug resistance gene （MDR1） are the molecular mechanisms of thegeneration of activity difference. In addition, the combination therapy, diet and other non-genetic factors are also an important reason for the ther- apeutic effect of CsA. This paper reviews the pharmacogenomics research of CsA combined with non-genetic factors, in order to provide ref- erence for clinical individualized medicine so as to ensure safety and rational use of drugs on pa- tients.