他克莫司的药物基因组学与个体化用药

Pharmacogenomics and personalized medicine of tacrolimus

他克莫司(FK506)是一种广泛应用的免疫抑制剂,在器官移植中发挥重要作用,由于治疗窗窄、个体间差异较大,常需要进行治疗药物监测。FK506是CYP3A酶和药物转运体P-糖蛋白(P-gp)的底物,CYP3A酶参与FK506的代谢而P-gp参与FK506的转运。这些酶的表达水平及生物活性差异可能会导致FK506个体间差异,而CYP3A及多药耐药基因(MDR1)基因多态性可能会影响CYP3A酶及P-gp的生物活性,所以CYP3A与MDR1基因多态性可能是造成FK506个体间差异的重要原因。本文就近年来FK506的药物基因组学研究进展加以综述。

Tacrolimus（FK506）,a widely used immunosuppressant,exerts a key effect in patients with organ transplantation.The drug requires therapeutic monitoring due to its narrow therapeutic index and great inter-individual variability.FK506 is known to be a substrate of CYP3A and P-glycoprotein（P-gp）.FK506 is metabolized by CYP3A and transported by P-gp.The difference in expression level and the bioactivity of these proteins may explain individual variations of FK506 pharmacokinetics.The differences in bioactivities of CYP3A and P-gp are believed to be due to CYP3A and MDR1 geneticmutation.Therefore,genetic variations of CYP3A and MDR1 may play an important role in the inter-individual variability of FK506.In this article,we reviewed the effect of CYP3A and MDR1 gene polymorphisms on pharmacokinetics of FK506 in patients with organ transplantation.This article presents an overview of the current research progress of pharmacogenomics of tacrolimus.