CYP3A5基因多态性对合用五酯软胶囊肾移植受者他克莫司剂量和血药浓度的影响  

Effect of CYP3A5 Gene Polymorphism on Dosage and Concentration of Tacrolimus inRenal Transplant Recipients Combined with Wuzhi Soft Capsule

作　　者：高丽[1] 王培乐[1] 贾萌萌[1] 杨晶[1] GAO Li;WANG Peile;JIA Mengmeng;YANG Jing(Department of Pharmacy,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院药学部,河南郑州450052

出　　处：《河南医学研究》2022年第11期1962-1965,共4页Henan Medical Research

摘　　要：目的探讨CYP3A5基因多态性对合用五酯软胶囊肾移植受者他克莫司用药剂量和血药浓度的影响,为肾移植患者合理应用他克莫司提供参考。方法回顾性分析郑州大学第一附属医院收治的154例肾移植受者,术后均接受他克莫司、糖皮质激素、吗替麦考酚酯和五酯软胶囊治疗方案,比较不同CYP3A5基因型患者达到治疗窗时的他克莫司给药剂量及谷浓度/剂量(C_(0)/D)值,以及术后3个月内急性排斥反应、肝损伤发生率。结果CYP3A5基因为*1/*1、*1/*3和*3/*3型的频率分别为6.49%、35.71%和57.79%。*3/*3型患者术后达到治疗窗时他克莫司的给药剂量为(0.076±0.019)mg·kg^(-1)·d^(-1),低于*1/*1和*1/*3型患者(P<0.001);*3/*3型患者的C_(0)/D为(150.32±49.96)[(μg/L)/(mg/d)],高于*1/*1和*1/*3型患者(P<0.001);3组患者术后3个月内急性排斥反应、肝功能异常、糖尿病发生率基本与基因分布频率相同。结论CYP3A5基因多态性与合用五酯软胶囊肾移植患者他克莫司的剂量和血药浓度具有显著的相关性,建议肾移植受者在用药前进行CYP3A5基因型分析。Objective To investigate the effect of CYP3A5 gene polymorphism on dosage and concentration on tacrolimus concentration in renal transplant recipients combined with Wuzhi soft capsule.Methods A total of 154 renal transplantat recipients who were treated in the First Affiliated Hospital of zhengzhou University were retrospectively analyzed.Patients received tacrolimus,mycophenolate,prednisolone and Wuzhi soft capsule postoperative.The tacrolimus dose and trough concentration/dose(C_(0)/D)values when tacrolimus concentration reached the therapeutic window were compared among different CYP3A5 genotypes,and the incidence rates of acute rejection and abnormal liver functions within 3 months after transplantation were also compared.Results The frequencies of CYP3A5*1/*1,*1/*3 and*3/*3 alleles in renal transplant patients were 6.49%、35.71%and 57.79%,respectively.When reached therapeutic window,the daily dose of tacrolimus in CYP3A5*3/*3 genotype group were(0.076±0.019)mg·kg^(-1)·d^(-1),which were lower than those in*1/*1 and*1/*3 genotype groups(P<0.001),and the C_(0)/D ratio of*3/*3 genotype group was(150.32±49.96)[(ng/mL)/(mg/d)],which was higher than those in*1/*1 and*1/*3 genotype groups(P<0.001).The incidence of acute rejection,abnormal liver function,and diabetes in three groups was almost the same as CYP3A5 gene frequency.Conclusion There was a significant correlation between CYP3A5 gene polymorphism and dosage and concentration of tacrolimus in renal transplant patients combined with Wuzhi soft capsule.Therefore,it is recommended that renal transplantation recipients undergo CYP3A5 genotype detection before treatment.

关 键 词：他克莫司 肾移植受者 CYP3A5基因 五酯软胶囊 血药浓度 

分 类 号：R969.1[医药卫生—药理学]