Practical Journal of Organ Transplantation(Electronic Version) ›› 2020, Vol. 8 ›› Issue (1): 27-32.DOI: 10.3969/j.issn.2095-5332.2020.01.006

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

Wang Xuebin 1,Xing Wenrong2,3,Zheng Shengnan4,Lu Hanlan5,Yang Yunyun1,Wang Zhuo1
  

  1. 1.Department ofPharmacy,Shanghai Changhai Hospital,Shanghai 200433,China ; 

    2. Department of Pharmacy,Children's Hospitalof Shanghai Jiaotong University,Shanghai 200062,China ; 

    3. Department of Pharmacy,Anhui Provincial Children'sHospital,Hefei 340111,Anhui,China;

    4. School of Pharmacy,Xuzhou Medical University,Xuzhou 221004,Jiangsu,China;

    5. Department of Organ Transplantation,Shanghai Changhai Hospital,Shanghai 200433,China

  • Online:2020-01-20 Published:2021-06-22

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

王学彬 1,邢文荣 2,3,郑胜男 4,陆瀚澜 5,杨云云 1,王卓 1   

  1. 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
  • 基金资助:

    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)

Abstract:

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 tacrolimusdose-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) wassignificantly lower than that of non-expressers (*3/*3) on day 3,7 and 14 after renal transplantation (P < 0.05). InCYP3A5 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 groupwas 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. 

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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 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。

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