Effects of <italic style="font-style: italic">CYP3A5</italic> gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients

XIANG Qiulin; LIU Ling; YANG Yi; LI Guoxing; CHEN Song; YANG Yingying; YU Xian

doi:10.6039/j.issn.1001-0408.2024.14.16

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Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients

更新时间：2024-07-25

- Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients
- ZHONGGUO YAOFANG Vol. 35, Issue 14, Pages: 1765-1769(2024)
- 作者机构：
  
  1.重庆医科大学附属第二医院Ⅰ期临床试验中心，重庆　400060
  2.重庆医科大学药学院，重庆　400016
  3.重庆医科大学附属第二医院泌尿肾病中心，重庆　400060
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.14.16
  CLC： R969.3;R968
- Published：30 July 2024，
  
  Received：19 January 2024，
  
  Revised：21 February 2024，
- 稿件说明：
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向秋林,刘玲,杨忆等.CYP3A5基因多态性及五酯胶囊对肾移植术后早期他克莫司暴露及不良反应的影响 ^Δ[J].中国药房,2024,35(14):1765-1769.

XIANG Qiulin,LIU Ling,YANG Yi,et al.Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients[J].ZHONGGUO YAOFANG,2024,35(14):1765-1769.
向秋林,刘玲,杨忆等.CYP3A5基因多态性及五酯胶囊对肾移植术后早期他克莫司暴露及不良反应的影响 ^Δ[J].中国药房,2024,35(14):1765-1769. DOI： 10.6039/j.issn.1001-0408.2024.14.16.

XIANG Qiulin,LIU Ling,YANG Yi,et al.Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients[J].ZHONGGUO YAOFANG,2024,35(14):1765-1769. DOI： 10.6039/j.issn.1001-0408.2024.14.16.

摘要

目的

探讨

CYP3A5

基因多态性及五酯胶囊（WZ）对肾移植患者术后早期他克莫司暴露及不良反应的影响。

方法

选择本院2021年9月至2023年9月接受同种异体肾移植术且术后接受他克莫司+霉酚酸类+泼尼松三联免疫治疗的患者132例为研究对象，根据其基因型（

CYP3A5

*1或

CYP3A5

*3/*3）和是否联用WZ（联用为“+WZ”，不联用为“+NO WZ”）将患者分为4组。分析4组患者在肾移植术后14 d、1个月、3个月的他克莫司血药谷浓度/日剂量（

）的差异，比较4组患者术后3个月内急性排斥反应及他克莫司相关不良反应的发生率。

结果

术后14 d、1个月、3个月（

CYP3A5

*1+WZ组患者除外），无论是否联用WZ，

CYP3A5

*1基因型患者的

均显著低于

CYP3A5

*3/*3基因型患者（

＜0.05）。4组患者术后3个月内，虽急性排斥反应及他克莫司相关不良反应发生率差异均无统计学意义（

＞0.05），但

CYP3A5

*3/*3+WZ组高血糖症发生率更高，达41.67%。

结论

CYP3A5

基因多态性与肾移植患者他克莫司

显著相关。在监测他克莫司

的前提下，

CYP3A5

*1基因型患者应在术后尽早联用WZ以加快他克莫司达到治疗浓度范围，而

CYP3A5

*3/*3基因型患者由于高血糖症发生风险较高，不推荐联用WZ。

Abstract

OBJECTIVE

To investigate the effects of

CYP3A5

gene polymorphism and Wuzhi capsule （WZ） on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients.

METHODS

A total of 132 patients who underwent renal

transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes （

CYP3A5

*1 or

CYP3A5

*3/*3） and with or without WZ （“+WZ” meant drug combination， “+NO WZ” meant without combination）. The blood trough concentration/daily dose （

） values of the four groups were analyzed on the 14th day， 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups.

RESULTS

On the 14th day， 1 month and 3 months after surgery （except for the

CYP3A5

*1+WZ group），

values of

CYP3A5

*1 genotype patients were significantly lower than those of

CYP3A5

*3/*3 genotype patients regardless of whether they were treated with WZ additionally （

＜0.05）. Within 3 months after surgery， although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups （

＞0.05）， the incidence of hyperglycemia in patients with

CYP3A5

*3/*3 was higher （41.67%）.

CONCLUSIONS

CYP3A5

gene polymorphism is significantly related to tacrolimus

in kidney transplant patients. Under the premise of

monitoring of tacrolimus， patients with

CYP3A5

*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range， while

CYP3A5

*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.

关键词

CYP3A5基因多态性五酯胶囊他克莫司肾移植不良反应

Keywords

gene polymorphismWuzhi capsuletacrolimusrenal transplantationadverse reactions

references

VINCENTI F，JENSIK S C，FILO R S，et al. A long-term comparison of tacrolimus（FK506） and cyclosporine in kidney transplantation：evidence for improved allograft survival at five years[J]. Transplantation，2002，73（5）：775-782.

EKBERG H，TEDESCO-SILVA H，DEMIRBAS A，et al. Reduced exposure to calcineurin inhibitors in renal transplantation[J]. N Engl J Med，2007，357（25）：2562-2575.

VENUTO R C，MEANEY C J，CHANG S，et al. Association of extrarenal adverse effects of posttransplant immuno-suppression with sex and ABCB1 haplotypes[J]. Medicine，2015，94（37）：e1315.

BOROBIA A M，ROMERO I，JIMENEZ C，et al. Trough tacrolimus concentrations in the first week after kidney transplantation are related to acute rejection[J]. Ther Drug Monit，2009，31（4）：436-442.

WALLEMACQ P，ARMSTRONG V W，BRUNET M，et al. Opportunities to optimize tacrolimus therapy in solid organ transplantation：report of the European consensus conference[J]. Ther Drug Monit，2009，31（2）：139-152.

WANG X B，YANG Y Y，LIU Z Y，et al. Switching immuno-suppression from cyclosporine to tacrolimus in kidney transplant recipients based on CYP3A5 genotyping[J]. Ther Drug Monit，2019，41（1）：97-101.

BIRDWELL K A，DECKER B，BARBARINO J M，et al. Clinical Pharmacogenetics Implementation Consortium（CPIC）guidelines for CYP3A5 genotype and tacrolimus dosing[J]. Clin Pharmacol Ther，2015，98（1）：19-24.

QIN X L，CHEN X，ZHONG G P，et al. Effect of tacrolimus on the pharmacokinetics of bioactive lignans of Wuzhi tablet（Schisandra sphenanthera extract）and the potential roles of CYP3A and P-gp[J]. Phytomedicine，2014，21（5）：766-772.

ZHANG H Y，BU F J，LI L，et al. Prediction of drug-drug interaction between tacrolimus and principal ingredients of Wuzhi capsule in Chinese healthy volunteers using physiologically-based pharmacokinetic modelling[J]. Basic Clin Pharmacol Toxicol，2018，122（3）：331-340.

杨燕，辛华雯，刘飞，等. 五酯胶囊对他克莫司增效作用与CYP3A5*3基因多态性的相关性研究[J]. 中国药房，2017，28（5）：581-585.

YANG Y，XIN H W，LIU F，et al. Study on the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 gene polymorphism[J]. China Pharm，2017，28（5）：581-585.

蔡宜朋，张宏，陈泉金，等. CYP3A5*3基因多态性与肾移植患者围手术期他克莫司相关不良反应的关系[J]. 中国医院药学杂志，2020，40（1）：87-90.

CAI Y P，ZHANG H，CHEN Q J，et al. The relationship between CYP3A5*3 gene polymorphism and tacrolimus-related adverse reactions in renal transplant patients du-ring perioperative period[J]. Chin J Hosp Pharm，2020，40（1）：87-90.

王一竹，柳芳，张相林. 五酯胶囊对肝、肾移植术后他克莫司治疗影响的系统评价[J]. 中国医院用药评价与分析，2021，21（6）：722-729.

WANG Y Z，LIU F，ZHANG X L. Systematic review of effects of Wuzhi capsules on tacrolimus treatment after liver and kidney transplantation[J]. Eval Anal Drug Use Hosp China，2021，21（6）：722-729.

PASSEY C，BIRNBAUM A K，BRUNDAGE R C，et al. Dosing equation for tacrolimus using genetic variants and clinical factors[J]. Br J Clin Pharmacol，2011，72（6）：948-957.

田普训，敖建华，李宁，等. 器官移植免疫抑制剂临床应用技术规范：2019版[J]. 器官移植，2019，10（3）：213-226.

TIAN P X，AO J H，LI N，et al. Technical specification for clinical application of immunosuppressive agents in organ transplantation：2019 edition[J]. Organ Transplant，2019，10（3）：213-226.

陈文倩，张雷，张弋，等. 实体器官移植他克莫司个体化治疗专家共识[J]. 中国医院用药评价与分析，2021，21（12）：1409-1424.

CHEN W Q，ZHANG L，ZHANG Y，et al. Expert consensus on individual treatment of tacrolimus in solid organ transplantation[J]. Eval Anal Drug Use Hosp China，2021，21（12）：1409-1424.

KNOPS N，LEVTCHENKO E，VAN DEN HEUVEL B，et al. From gut to kidney：transporting and metabolizing calcineurin-inhibitors in solid organ transplantation[J]. Int J Pharm，2013，452（1/2）：14-35.

STAATZ C E，GOODMAN L K，TETT S E. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors：part Ⅰ[J]. Clin Pharmacokinet，2010，49（3）：141-175.

李嘉丽，王雪丁，王长希，等. CYP3A5*3基因型联合五酯片干预他克莫司用药的前瞻性研究[C]// 中国药理学会临床药理专业委员会.第十二次全国临床药理学学术会议会议论文集.中山：中山大学临床药理研究所，2010：297-299.

LI J L，WANG X D，WANG C X，et al.A prospective study on the intervention of CYP3A5*3 genotype combined with pentaester tablets in tacrolimus medication [C]//Committee of Clinical Pharmacology Chinese Pharmacological Society. Proceedings of the 12th National Conference on Clinical Pharmacology. Zhongshan：Institute of Clinical Pharmacology，Sun Yat-sen University，2010：297-299.

冯玘，杨春兰，冯丽娟，等. 肾移植患者基因多态性对五酯胶囊增加他克莫司血药浓度的影响[J]. 中国药房，2020，31（4）：477-484.

FENG Q，YANG C L，FENG L J，et al. Effects of gene polymorphism on the increasing of tacrolimus blood concentration induced by Wuzhi capsules in renal transplantation patients[J]. China Pharm，2020，31（4）：477-484.

李新长，孟栋良，龙成美，等. 肾移植受者CYP3A5基因多态性对他克莫司血药浓度及疗效的影响[J]. 中国组织工程研究，2012，16（18）：3255-3258.

LI X C，MENG D L，LONG C M，et al. Effect of CYP3A5 genetic polymorphism on concentration and efficacy of tacrolimus in patients with kidney transplantation[J]. Chin J Tissue Eng Res，2012，16（18）：3255-3258.

侯明明，宋洪涛，王庆华，等. 肾移植患者CYP3A5*3基因多态性对他克莫司血药浓度/剂量比和疗效的影响[J]. 中国医院药学杂志，2010，30（4）：313-316.

HOU M M，SONG H T，WANG Q H，et al. Effect of CYP3A5*3 genetic polymorphism on concentration/dose and efficacy of tacrolimus in patients with kidney transplantation[J]. Chin J Hosp Pharm，2010，30（4）：313-316.

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Effects of CYP3A5 gene polymorphism and Wuzhi capsule on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients

DOI：10.6039/j.issn.1001-0408.2024.14.16

摘要

Abstract

关键词

Keywords

references