[1]宋学武,高慧儿,张飞雨,等.CYP3A4多态性对活体肝移植患儿术后早期他克莫司浓度/剂量比和个体内变异度的影响[J].天津医科大学学报,2021,27(04):388-391.
SONG Xue-wu,GAO Hui-er,ZHANG Fei-yu,et al.Effect of CYP3A4 polymorphism on tacrolimus concentration to dose ratio and intra-patient variability in the early postoperative period for infant patients with living donor liver transplantation[J].Journal of Tianjin Medical University,2021,27(04):388-391.
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CYP3A4多态性对活体肝移植患儿术后早期他克莫司浓度/剂量比和个体内变异度的影响(PDF)
《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]
- 卷:
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27卷
- 期数:
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2021年04期
- 页码:
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388-391
- 栏目:
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临床医学
- 出版日期:
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2021-07-20
文章信息/Info
- Title:
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Effect of CYP3A4 polymorphism on tacrolimus concentration to dose ratio and intra-patient variability in the early postoperative period for infant patients with living donor liver transplantation
- 文章编号:
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1006-8147(2021)04-0388-04
- 作者:
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宋学武1; 高慧儿2; 张飞雨1; 秦寅鹏2; 张弋2
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(1.天津医科大学一中心临床学院,天津 300192;2.天津市第一中心医院药学部,南开大学医学院,天津 300192)
- Author(s):
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SONG Xue-wu1; GAO Hui-er2; ZHANG Fei-yu1; QIN Yin-peng2; ZHANG Yi2
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(1. First Central Clinical College, Tianjin Medical University, Tianjin 300192,China;2. Department of Pharmacy, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China)
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- 关键词:
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活体肝移植; 他克莫司; CYP3A4; 浓度/剂量比; 个体内变异度
- Keywords:
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living donor liver transplantation; tacrolimus; CYP3A4; concentration to dose ratio; intra-patient variability
- 分类号:
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R781.4
- DOI:
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- 文献标志码:
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A
- 摘要:
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目的:探讨供、受者CYP3A4多态性对活体肝移植(LDLT)患儿术后1个月内他克莫司浓度/剂量比(C0/D)和个体内变异度(IPV)的影响。方法:收集77例活体肝移植患儿,化学发光免疫分析法测定他克莫司谷浓度(C0)。检测供、受者CYP3A4*18B基因型,根据患者至少携带一个CYP3A4*1基因将患者分为两组,即CYP3A4表达组(EX,CYP3A4*1/*1或CYP3A4*1/*18B)和CYP3A4非表达组(NEX,CYP3A4*18B/*18B)。分析CYP3A4*18B多态性对不同基因型患者他克莫司C0/D和IPV的影响。结果:对于供者CYP3A4多态性,CYP3A4表达组他克莫司C0/D在术后第1周(Z=-4.694,P<0.001)、第2周(Z=-4.469,P<0.01)和第3周(Z=-2.205,P<0.05)均显著低于CYP3A4非表达组;对于受者CYP3A4多态性,CYP3A4表达组他克莫司C0/D在术后第1周(Z=-4.976,P<0.001)和第2周(Z=-3.054,P<0.01)均显著低于CYP3A4非表达组。此外,供、受者CYP3A4表达组与CYP3A4非表达组他克莫司IPV均无差异(均P>0.05)。结论:CYP3A4多态性影响LDLT患儿术后早期他克莫司C0/D,对他克莫司IPV没有影响。
- Abstract:
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Objective: To investigate the effectof donors′ and recipients′ CYP3A4 polymorphisms on tacrolimus concentration to dose ratio(C0/D) and intra-patient variability(IPV) within one month for infant patients with living donor liver transplantation(LDLT). Methods: A total of 77 infant patients with LDLT were collected. Tacrolimus trough concentration(C0) was determined by chemiluminescent microparticle immunoassay.The donors′ and recipients′ CYP3A4*18B genotypes were detected.According to individuals with at least one CYP3A4*1 allele,patients were divided into two groups including CYP3A4 expressers(EX,CYP3A4*1/*1 or CYP3A4*1/*18B) and CYP3A4 non-expressers(NEX,CYP3A4*18B/*18B).The effect of CYP3A4*18B polymorphism on tacrolimus C0/D and IPV in patients with different genotypes was analyzed. Results: For the donors′ CYP3A4 polymorphism,tacrolimus C0/D in CYP3A4 expressers was significantly lower than that in CYP3A4 non-expressers in the first week(Z=-4.694,P<0.001),second week(Z=-4.469,P<0.01),and third week(Z=-2.205,P<0.05) after transplantation. For the recipients′ CYP3A4 polymorphism, tacrolimus C0/D in CYP3A4 expressers was significantly lower than that in CYP3A4 non-expressers in the first week(Z=-4.976,P<0.001) and second week(Z=-3.054,P<0.01) after transplantation. In addition, there was no difference in tacrolimus IPV between CYP3A4 expressers and CYP3A4 non-expressers(all P>0.05). Conclusion: The CYP3A4 polymorphism has an effect on tacrolimus C0/D for infant patients with LDLT in the early postoperative period,but has no effect on tacrolimus IPV.
参考文献/References:
[1] Brunet M,Van Gelder T,?魡sberg A, et al.Therapeutic drug monitoring of tacrolimus-personalized therapy:second consensus report[J].Ther Drug Monit,2019,41(3):261
[2] Shuker N,Shuker L,VanRosmalen J,et al.A high intrapatient variability in tacrolimus exposure is associated with poor long-term outcome of kidney transplantation[J].Transpl Int,2016,29(11):1158
[3] Musuamba F T,Guy-Viterbo V,Reding R,et al.Population pharmacokinetic analysis of tacrolimus early after pediatric liver transplantation[J].Ther Drug Monit,2014,36(1):54
[4] Kasahara M,Sakamoto S,Sasaki K,et al.Living donor liver transplantation during the first 3 months of life[J].Liver Transpl,2017, 23(8):1051
[5] Liu B Y,Chen W Q,Chen Z G,et al.The effects of CYP3A5 genetic polymorphisms on serum tacrolimus dose-adjusted concentrations and long-term prognosis in Chinese heart transplantation recipients[J]. Eur J Drug Metab Pharmacokinet,2019,44(6):771
[6] Pashaee N,Bouamar R,Hesselink D,et al. CYP3A5 genotype is not related to the intrapatient variability of tacrolimus clearance[J]. Ther Drug Monit,2011,33(3):369
[7] Nadalin S,Capobianco I,Panaro F, et al. Living donor liver transplantation in Europe[J].Hepatobiliary Surg Nutr,2016,5(2):159
[8] Cuenca A G,Kim H B,VakiliK.Pediatric liver transplantation[J].Semin Pediatr Surg,2017,26(4):217
[9] 中华医学会器官移植学分会, 中国医师协会器官移植医师分会. 中国儿童肝移植临床诊疗指南(2015版)[J]. 临床肝胆病杂志, 2016,32(7):1235
[10] 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
[11] Ji E,Choi L,Suh K S, et al.Combinational effect of intestinal and hepatic CYP3A5 genotypes on tacrolimus pharmacokinetics in recipients of living donor liver transplantation[J].Transplantation,2012,94(8):866
[12] Hendijani F,Azarpira N,Kaviani M. Effect of CYP3A5*1 expression on tacrolimus required dose after liver transplantation:a systematic review and meta-analysis[J].Clin Transplant,2018,32(8):e13306
[13] Lloberas N,Elens L,Llaudó I, et al.The combination of CYP3A4*22 and CYP3A5*3 single-nucleotide polymorphisms determines tacrolimus dose requirement after kidney transplantation[J].Pharmacogenet Genomics,2017,27(9):313
[14] Abdel-Kahaar E,Winter S,Tremmel R,et al.The impact of CYP3A4*22 on tacrolimus pharmacokinetics and outcome in clinical practice at a single kidney transplant center[J].Front Genet,2019,10:871
[15] Werk A N,Cascorbi I. Functional gene variants of CYP3A4[J].ClinPharmacol Ther,2014,96(3):340
[16] 朱琳,宋洪涛,王庆华,等.CYP3A4*18B和CYP3A5*3基因多态性对肾移植患者他克莫司剂量及浓度的影响[J].药学学报,2012,47(7):878
[17] Tamashiro E Y,Felipe C R,Genvigir F, et al.Influence of CYP3A4 and CYP3A5 polymorphisms on tacrolimus and sirolimus exposure in stable kidney transplant recipients[J].Drug Metab Pers Ther,2017,
32(2):89
[18] Gijsen V,Mital S,Van Schaik R H, et al.Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients[J]. J Heart Lung Transplant,2011,30(12):1352
[19] Przepiorka D,Blamble D,Hilsenbeck S, et al.Tacrolimus clearance is age-dependent within the pediatric population[J].Bone Marrow Transplant,2000,26(6):601
[20] Cheung C Y,Chan K M,Wong Y T, et al.Impact of CYP3A5 genetic polymorphism on intrapatient variability of tacrolimus exposure in Chinese kidney transplant recipients[J].Transplant Proc,2019, 51(6):1754
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[1]薛志杰综述,王荔,杨虎,等.特发性膜性肾病的临床治疗进展[J].天津医科大学学报,2022,28(03):336.
备注/Memo
- 备注/Memo:
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基金项目:白求恩·医学科学研究基金项目(TA201933);天津市卫生健康科技项目(KJ20226)
作者简介:宋学武(1995-),男,硕士在读,研究方向:临床药学;通信作者:张弋,E-mail: wing_zh1821@sina.com。
更新日期/Last Update:
2021-07-25