器官移植受者体内他克莫司膜转运体的遗传药理学研究进展

Advances in Pharmacogenetics of Tacrolimus Membrane Transporters in Organ Transplant Recipients

他克莫司作为一种新型免疫抑制剂,广泛应用于各类器官移植的治疗中,效果显著。他克莫司具有很强的个体代谢差异性,治疗窗窄,给药剂量难以在合理的范围内,引起术后移植功能不全,不良反应多发,严重降低了移植器官的生存率。代谢酶是影响他克莫司代谢的重要遗传因素,此外,转运体也与他克莫司代谢密切相关,对转运体的基因多态性进行研究,对他克莫司的疗效分析具有重要意义。该文综述了他克莫司体内主要摄取或外排转运体,主要包括P-gp、MRP、OATP、ZnT8和CNT3对他克莫司的疗效以及不良反应的影响,部分研究结论可指导临床用药,为器官移植患者个体化治疗提供参考。

Tacrolimus,as a new immunosuppressant,has been widely used in the prognosis of various organ transplantation with remarkable therapeutic effect.In the long-term clinical use,it was found that tacrolimus had a strong individual metabolic differences and narrow therapeutic window,which made it difficult to give a reasonable administraion dose,resulting in postoperative transplantation dysfunction and multiple adverse reactions,thus seriously reducing the survival rate of transplanted organs.Studies have shown that metabolic enzymes are important genetic factors affecting tacrolimus metabolism.In addition,transporters are also closely related to tacrolimus metabolism.The study of gene polymorphism of transporters is of great significance for the efficacy of tacrolimus.This paper reviews the main uptake or efflux transporters of tacrolimus,mainly including the effects of P-gp,MRP,OATP,ZnT8 and CNT3 on the efficacy and adverse reactions of tacrolimus.Some research conclusions can guide clinical medication and provide basis for the personalized treatment of organ transplantation patients.