五酯胶囊和CYP3A5*3多态性与肾移植术后早期他克莫司血药浓度相关性研究  

Association of wuzhi capsule and CYP3A5*3 genetic polymorphism with tacrolimus blood concentration of renal transplant recipients during the early stage after transplantation

作　　者：王学彬[1] 邢文荣[2,3] 郑胜男 陆瀚澜 杨云云 王卓[1] Wang Xuebin;Xing Wenrong;Zheng Shengnan;Lu Hanlan;Yang Yunyun;Wang Zhuo(Department of Pharmacy,Shanghai Changhai Hospital,Shanghai 200433,China;Department of Pharmacy,Children's Hospital of Shanghai Jiaotong University,Shanghai 200062,China;Department of Pharmacy,Anhui Provincial Children's Hospital,Hefei 340111,Anhui,China;School of Pharmacy,Xuzhou Medical University,Xuzhou 221004,Jiangsu,China;Department of Organ Transplantation,Shanghai Changhai Hospital,Shanghai 200433,China)

机构地区：[1]上海长海医院药学部,上海200433 [2]上海交通大学附属儿童医院药学部,上海200062 [3]安徽省儿童医院药学部,安徽合肥340111 [4]徐州医科大学药学院,江苏徐州221004 [5]上海长海医院器官移植科,上海200433

出　　处：《实用器官移植电子杂志》2020年第1期27-32,共6页Practical Journal of Organ Transplantation(Electronic Version)

基　　金：上海市“医苑新星”青年医学人才培养资助计划(沪卫计人事[2019]72号);上海交通大学医学院2017年度医院药学科研基金青年项目(JDYX2017QN016);国家自然科学基金项目(81870520);2018年医院教学研究与改革项目(CHJG201812)。

摘　　要：目的探究五酯胶囊联合CYP3A5*3多态性对肾移植受者术后早期他克莫司血药谷浓度(trough concentration,C0)的影响。方法通过聚合酶链反应-限制性片段长度多态性法(polymerase chain reaction-restriction fragement length polymorphism,PCR-RFLP)测定CYP3A5*3基因型。利用化学发光免疫分析法(chemiluminescence immunoassay,CMIA)法测定他克莫司C0。分析五酯胶囊不同日剂量(dose,D)及CYP3A5*3基因型对肾移植受者术后早期他克莫司剂量调整血药谷浓度(dose-adjusted trough concentration,C0/D)的影响。结果五酯胶囊各日剂量组(0、22.5和45 mg)在术后第3、7和14天,CYP3A5表达者(*1/*1+*1/*3)的他克莫司C0/D显著低于非表达者(*3/*3)(P<0.05)。CYP3A5表达者在第3、7和14天,五酯胶囊各组(0、22.5和45 mg)的C0/D有显著性差异(P<0.05)。然而,第14天CYP3A5表达者五酯胶囊67.5 mg组的C0/D却显著低于22.5 mg和45 mg组(P>0.05),且CYP3A5非表达者五酯胶囊45 mg组的C0/D显著低于22.5 mg组(P<0.05)。结论CYP3A5表达的肾移植受者术后早期可联用五酯胶囊(最大日剂量44.5 mg),用于提升他克莫司浓度和降低药费。Objective To investigate the effect of wuzhi capsule combined with CYP3A5*3 genetic polymorphism on the tacrolimus blood trough concentration(C0)of renal transplant recipients in the early post transplant stage.Methods CYP3A5*3 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Tacrolimus C0 was tested using chemiluminescence immunoassay(CMIA).The effect of both the daily dose(D)of wuzhi capsule and CYP3A5*3 genotype on the tacrolimus dose-adjusted trough concentration(C0/D)was evaluated in the early post transplant stage.Results Among all of the different wuzhi capsule groups(0,22.5 and 45 mg),tacrolimus C0/D of CYP3A5 expressers(*1/*1+*1/*3)was significantly lower than that of non-expressers(*3/*3)on day 3,7 and 14 after renal transplantation(P<0.05).In CYP3A5 expressers on day 3,7 and 14,there were significant differences of tacrolimus C0/D among different wuzhi capluse groups(0,22.5 and 45 mg).However,on day 14,tacrolimus C0/D with 67.5 mg wuzhi capsule group was significantly lower than those of both 22.5 mg and 45 mg groups(P>0.05),and tacrolimus C0/D with 45 mg group was significantly lower than that of 22.5 mg group(P>0.05).Conclusion For renal transplant recipients with CYP3A5 express,wuzhi capsule could be used to increase the blood concentration of tacrolimus and reduce its costs in the early stage after transplantation.

关 键 词：肾移植 他克莫司 五酯胶囊 CYP3A5*3 治疗药物监测 

分 类 号：R699.2[医药卫生—泌尿科学]