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Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients

CYP3A5 genetic variants are associated with tacrolimus metabolism. Controversy remains on whether CYP3A4 increased [* 1B (rs2740574), *1G (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This study aims to address whether tacrolimus dose-adjuste...

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Autores principales: Hernandez, Savine, Aquilante, Christina, Deininger, Kimberly, Lindenfeld, Joann, Schlendorf, Kelly, Van Driest, Sara, Liu, Michelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246090/
https://www.ncbi.nlm.nih.gov/pubmed/37292893
http://dx.doi.org/10.21203/rs.3.rs-2921796/v1
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author Hernandez, Savine
Aquilante, Christina
Deininger, Kimberly
Lindenfeld, Joann
Schlendorf, Kelly
Van Driest, Sara
Liu, Michelle
author_facet Hernandez, Savine
Aquilante, Christina
Deininger, Kimberly
Lindenfeld, Joann
Schlendorf, Kelly
Van Driest, Sara
Liu, Michelle
author_sort Hernandez, Savine
collection PubMed
description CYP3A5 genetic variants are associated with tacrolimus metabolism. Controversy remains on whether CYP3A4 increased [* 1B (rs2740574), *1G (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*7Bor *7G variants (Group 3) compared to CYP3A4*1/*1 (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients.
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spelling pubmed-102460902023-06-08 Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients Hernandez, Savine Aquilante, Christina Deininger, Kimberly Lindenfeld, Joann Schlendorf, Kelly Van Driest, Sara Liu, Michelle Res Sq Article CYP3A5 genetic variants are associated with tacrolimus metabolism. Controversy remains on whether CYP3A4 increased [* 1B (rs2740574), *1G (rs2242480)] and decreased function [*22 (rs35599367)] genetic variants provide additional information. This study aims to address whether tacrolimus dose-adjusted trough concentrations differ between combined CYP3A (CYP3A5 and CYP3A4) phenotype groups. Significant differences between CYP3A phenotype groups in tacrolimus dose-adjusted trough concentrations were found in the early postoperative period and continued to 6 months post-transplant. In CYP3A5 nonexpressers, carriers of CYP3A4*7Bor *7G variants (Group 3) compared to CYP3A4*1/*1 (Group 2) patients were found to have lower tacrolimus dose-adjusted trough concentrations at 2 months. In addition, significant differences were found among CYP3A phenotype groups in the dose at discharge and time to therapeutic range while time in therapeutic range was not significantly different. A combined CYP3A phenotype interpretation may provide more nuanced genotype-guided TAC dosing in heart transplant recipients. American Journal Experts 2023-05-16 /pmc/articles/PMC10246090/ /pubmed/37292893 http://dx.doi.org/10.21203/rs.3.rs-2921796/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. https://creativecommons.org/licenses/by/4.0/License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License (https://creativecommons.org/licenses/by/4.0/)
spellingShingle Article
Hernandez, Savine
Aquilante, Christina
Deininger, Kimberly
Lindenfeld, Joann
Schlendorf, Kelly
Van Driest, Sara
Liu, Michelle
Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients
title Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients
title_full Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients
title_fullStr Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients
title_full_unstemmed Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients
title_short Composite CYP3A (CYP3A4 and CYP3A5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients
title_sort composite cyp3a (cyp3a4 and cyp3a5) phenotypes and influences on tacrolimus dose adjusted concentration in adult heart transplant recipients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10246090/
https://www.ncbi.nlm.nih.gov/pubmed/37292893
http://dx.doi.org/10.21203/rs.3.rs-2921796/v1
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