CYP3A4*22 and CYP3A combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients

被引：4
|
作者：
Gijsen, Violette M. G. J. [1 ,2 ]
van Schaik, Ron H. N. [3 ]
Elens, Laure [3 ,4 ]
Soldin, Offie P. [5 ]
Soldin, Steven J. [5 ]
Koren, Gideon [2 ,6 ]
de Wildt, Saskia N. [1 ]
机构：
[1] Erasmus MC Sophia Childrens Hosp, Dept Pediat Surg & Intens Care, NL-3015 GJ Rotterdam, Netherlands
[2] Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON M5G 1X8, Canada
[3] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands
[4] Catholic Univ Louvain, Louvain Ctr Toxicol & Appl Pharmacol LTAP, B-1200 Brussels, Belgium
[5] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA
[6] Univ Western Ontario, Dept Med, London, ON, Canada
来源：
PHARMACOGENOMICS | 2013年 / 14卷 / 09期
关键词：
children; CYP3A4*22; heart transplantation; pharmacogenetics; tacrolimus; DOSE REQUIREMENTS; DRUG-METABOLISM; PHARMACOKINETICS; POLYMORPHISMS; CYCLOSPORINE; EXPRESSION; CAUCASIANS; CHILDREN; INFANTS; ENZYMES;
D O I：
10.2217/PGS.13.80
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Background: Tacrolimus metabolism depends on CYP3A4 and CYP3A5. We aimed to determine the relationship between the CYP3A4*22 polymorphism and combined CYP3A genotypes with tacrolimus disposition in pediatric heart transplant recipients. Methods: Sixty pediatric heart transplant recipients were included. Tacrolimus doses and trough concentrations were collected in the first 14 days post-transplantation. CYP3A phenotypes were defined as extensive (CYP3A5*1 + CYP3A4*1/*1 carriers), intermediate (CYP3A5*3/*3 + CYP3A4*1/*1 carriers) or poor (CYP3A5*3/*3 + CYP3A4*22 carriers) metabolizers. Results:CYP3A4*22 carriers needed 30% less tacrolimus (p = 0.016) to reach similar target concentrations compared with CYP3A4*1/*1 (n = 56) carriers. Poor CYP3A metabolizers required 17% (p = 0.023) less tacrolimus than intermediate and 48% less (p < 0.0001) than extensive metabolizers. Poor metabolizers showed 18% higher dose-adjusted concentrations than intermediate (p = 0.35) and 193% higher than extensive metabolizers (p < 0.0001). Conclusion: Analysis of CYP3A4*22, either alone or in combination with CYP3A5*3, may help towards individualization of tacrolimus therapy in pediatric heart transplant patients.
引用
收藏
页码：1027 / 1036
页数：10
相关论文
共 50 条
  • [1] Effect of CYP3A4*22 and CYP3A5 Combined Genotypes on Tacrolimus Disposition in Heart Transplantation
    Vu, A.
    Page, R. L.
    Roscoe, N.
    Lindenfeld, J. A.
    Aquilante, C. L.
    JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2014, 33 (04): : S115 - S116
  • [2] CYP3A pharmacogenetics and tacrolimus disposition in adult heart transplant recipients
    Deininger, Kimberly M.
    Vu, Anh
    Page, Robert L., II
    Ambardekar, Amrut V.
    Lindenfeld, JoAnn
    Aquilante, Christina L.
    CLINICAL TRANSPLANTATION, 2016, 30 (09) : 1074 - 1081
  • [3] Effect of CYP3A4* 22, CYP3A5* 3, and CYP3A Combined Genotypes on Cyclosporine, Everolimus, and Tacrolimus Pharmacokinetics in Renal Transplantation
    Moes, D. J. A. R.
    Swen, J. J.
    den Hartigh, J.
    van der Straaten, T.
    van der Heide, J. J. Homan
    Sanders, J. S.
    Bemelman, F. J.
    de Fijter, J. W.
    Guchelaar, H. J.
    CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, 2014, 3 (02):
  • [4] CYP3A4/5 genotypes and age codetermine tacrolimus concentration and dosage in pediatric heart transplant recipients
    Liu, Li
    Huang, Xiao
    Zhou, Ying
    Han, Yong
    Zhang, Jing
    Zeng, Fang
    Huang, Yifei
    Zhou, Hong
    Zhang, Yu
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2022, 111
  • [5] Effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on tamoxifen metabolism
    A. B. Sanchez Spitman
    D. J. A. R. Moes
    H. Gelderblom
    V. O. Dezentje
    J.J. Swen
    H. J. Guchelaar
    European Journal of Clinical Pharmacology, 2017, 73 : 1589 - 1598
  • [6] Effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on tamoxifen metabolism
    Spitman, A. B. Sanchez
    Moes, D. J. A. R.
    Gelderblom, H.
    Dezentje, V. O.
    Swen, J. J.
    Guchelaar, H. J.
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2017, 73 (12) : 1589 - 1598
  • [7] Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influence on tacrolimus dose adjusted concentrations in adult heart transplant recipients
    Michelle Liu
    Savine Hernandez
    Christina L. Aquilante
    Kimberly M. Deininger
    Joann Lindenfeld
    Kelly H. Schlendorf
    Sara L. Van Driest
    The Pharmacogenomics Journal, 2024, 24
  • [8] Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influence on tacrolimus dose adjusted concentrations in adult heart transplant recipients
    Liu, Michelle
    Hernandez, Savine
    Aquilante, Christina L.
    Deininger, Kimberly M.
    Lindenfeld, Joann
    Schlendorf, Kelly H.
    Van Driest, Sara L.
    PHARMACOGENOMICS JOURNAL, 2024, 24 (02):
  • [9] The distribution of MDR1, CYP3A4 and CYP3A5 genotypes in a polish heart transplant recipients
    Kunicki, Pawel K.
    Sobieszczanska-Malek, Malgorzata
    Gmik, Wanda
    Drozdzik, Marek
    Adler, Grazyna
    Ciechanowicz, Andrzej
    THERAPEUTIC DRUG MONITORING, 2007, 29 (04) : 545 - 545
  • [10] Description of CYP3A4*22 and CYP3A5*3 frequencies and impact on first tacrolimus (TAC) doses in renal transplant recipients
    Lori, L.
    Zaidan, M.
    Furlan, V.
    Bouligand, J.
    Becquemont, L.
    Verstuyft, C.
    FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2021, 35 : 159 - 160
12345