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基于CYP3A5、MDR1基因多态性的公式化用药对肾移植术后早期他克莫司用药的指导意义

The individualized formular administration of tacrolimus after kidney transplantation based on the CYP3A5 and MDR1 gene polymorphism

摘要:

目的 探讨基于CYP3A5、MDR1基因多态性的公式化用药对肾移植术后早期他克莫司用药的可行性和临床指导意义.方法 选择2015年10月1日至2016年7月30日肾移植受者129例,随机分成2组:实验组65例、对照组64例.实验组用焦磷酸测序法检测CYP3A5、MDR1基因多态性,并根据公式计算出他克莫司的用量,对照组根据体重经验性用药.服用他克莫司3天后,检测他克莫司浓度谷值,比较两组浓度的差异,及术后1周受者肾功能恢复情况、急性排斥反应及透析情况的差异.结果 术后首次他克莫司浓度:实验组平均为(9.24±2.32) μg/L,对照组平均为(9.39±3.47)μg/L.实验组有7例不在正常范围之内,对照组有18例不在正常范围(P<0.0)5).术后1周肌酐水平,实验组为(157.36±110.55)μg/L和(174.01±130.68)μg/L(P>0.05).实验组有2例发生急性排斥反应,对照组有5例发生急性排斥反应,P>0.05.实验组有4例术后1周内需要透析治疗,对照组有10例,P<0.05,差异有统计学意义.结论 基于CYP3A5、MDR1基因多态性的公式化用药较经验性用药更加合理,使他克莫司浓度更易于达到正常范围,有利于肾移植术后的早期恢复.

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Objective To explore the feasibility and clinical significance of individualized formular administration of tacrolimus after renal transplantation based on the CYP3A5 and MDR1 gene polymorphism.Methods Total 129 renal transplantation recipients from Oct.1,2015 to July 30,2016 were included in this study and divided into 2 groups.In experimental group,tacrolimus was administrated by the individualized formula based on CYP3A5 and MDR1 gene polymorphism;in control group,tacrolimus was administrated by doctors' experience based on patient's body weight.The blood trough level of tacrolimus was determined 3 days after administration.The first blood trough level of tacrolimus,plasma creatinine level,acute rejection rate,and necessity for dialysis were compared between two groups.Results The first blood trough levels of tacrolimus in experimental and control groups were 9.24 ± 2.32 and 9.39 ± 3.47μg/L respectively (P>0.05).The tacrolimus levels of 7 cases in experimental group and 18 cases in control group were not in normal range (P<0.05).The plasma creatinine level at day 7 after surgery was 157.36 ± 110.55 μg/L in experimental group,and 174.01 ± 130.68μg/L in control group (P>0.05).Acute rejection was found in both two groups:2 in experimental group and 5 in control group (P > 0.05).There was significant difference in necessity for dialysis between two groups:4 in experimental group and 10 in control group (P<0.05).Conclusion The individualized formular administration of tacrolimus based on the CYP3A5 and MDR1 gene polymorphism is more feasible and reasonable than experimental administration,which is more easier to come to an appropriate blood level and would benefit the early recovery of renal function.

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