他克莫司缓释胶囊在CYP3A5不同基因型肾移植受者中浓度/剂量值的差异

Differences of Concentration/Dose of Tacrolimus Sustained-Release Capsules in Kidney Transplant Recipients with Different CYP3A5 Genotypes

目的探讨他克莫司缓释胶囊在CYP3A5不同基因型肾移植受者中他克莫司浓度/剂量值(C_(0)/D)的变化特点。方法回顾性分析2019年8月至2020年2月在郑州大学第一附属医院行肾移植手术且术后采用免疫抑制方案(他克莫司缓释胶囊、吗替麦考酚酯联合甲泼尼龙)的31例成人肾移植受者。所有受者术前均检测CYP3A5基因型,分别把基因型为CYP3A5*1/*1、*1/*3的受者分为快代谢组,*3/*3型分为慢代谢组。记录术后不同时间点(第3、7、14天及第1、2、4、6、8、10、12个月)受者他克莫司谷浓度,计算C_(0)/D,比较两组C_(0)/D值的差异,对比不良反应的发生率。结果慢代谢组受者的C 0/D在术后第3、7、14天及第1、2、4、6、8、10、12个月均高于快代谢组受者,且在第7天及第2、6、8、10、12个月的差异有统计学意义(P<0.05)。两组患者总不良反应发生率比较,差异无统计学意义(P>0.05)。结论不同CYP3A5基因对肾移植术后口服他克莫司缓释胶囊患者的C_(0)/D值有影响,应根据CYP3A5基因型进行个体化给药。

Objective To investigate the differences of concentration/dose(C 0/D)of tacrolimus sustained-release capsules in renal transplant recipients with different CYP3A5 genotypes.Methods A retrospective analysis was made on 31 adult renal transplant recipients who underwent renal transplantation in the First Affiliated Hospital of Zhengzhou University from August 2019 to February 2020 and received immunosuppressive regimens(tacrolimus sustained release capsule and mycophenolate mofetil and methylprednisolone).The CYP3A5 genotypes of all recipients were detected before operation.Patients with genotypes CYP3A5*1/*1,*1/*3 were divided into the fast metabolizer group,and*3/*3 patients were divided into the slow metabolizer group.The concentration of tacrolimus was recorded at different time points(3,7,14 days and 1,2,4,6,8,10,12 months after operation),and the C_(0)/D value was calculated.The difference of C_(0)/D value between the two groups was compared,and the incidence of adverse reactions was compared.Results The C_(0)/D value of slow metabolizing recipients was higher than that of fast metabolizing recipients at 3,7,14 days and 1,2,4,6,8,10,12 months after surgery,and there were differences at 7 d,2,6,8,10,and 12 month(P<0.05).There was no difference in the incidence of total adverse reactions between the two groups of patients(P>0.05).Conclusion The difference of CYP3A5 genotypes in recipients has influence on the C_(0)/D value after tacrolimus sustained-release capsules.Individual administration based on the difference of CYP3A5 genotypes is necessary in renal transplant recipients.