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Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy

BACKGROUND: Tacrolimus (TAC) is beneficial for patients with idiopathic membranous nephropathy (IMN). It has a narrow therapeutic concentration range and many factors influence TAC blood concentration. CYP3A5 is the most important enzyme in TAC metabolism. The aim of this study was to analyze the ef...

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Autores principales: Zhang, Chengning, Duan, Suyan, Guo, Miao, Yuan, Yanggang, Huang, Zhimin, Zhu, Jingfeng, Sun, Bin, Zhang, Bo, Xing, Changying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186213/
https://www.ncbi.nlm.nih.gov/pubmed/32368128
http://dx.doi.org/10.2147/PGPM.S247892
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author Zhang, Chengning
Duan, Suyan
Guo, Miao
Yuan, Yanggang
Huang, Zhimin
Zhu, Jingfeng
Sun, Bin
Zhang, Bo
Xing, Changying
author_facet Zhang, Chengning
Duan, Suyan
Guo, Miao
Yuan, Yanggang
Huang, Zhimin
Zhu, Jingfeng
Sun, Bin
Zhang, Bo
Xing, Changying
author_sort Zhang, Chengning
collection PubMed
description BACKGROUND: Tacrolimus (TAC) is beneficial for patients with idiopathic membranous nephropathy (IMN). It has a narrow therapeutic concentration range and many factors influence TAC blood concentration. CYP3A5 is the most important enzyme in TAC metabolism. The aim of this study was to analyze the effects of CYP3A5 gene polymorphisms on the efficacy and safety of TAC in IMN patients. PATIENTS AND METHODS: Patients with IMN who received oral TAC (0.05–0.075mg/kg/day) combined with prednisone (0.5mg/kg/day) from March 2016 to October 2018 were included. The data of clinical characteristics, therapeutic drugs and adverse reactions of patients were collected at baseline and during 24 weeks of treatment. Patients were divided into two groups according to different CYP3A5 genetic polymorphisms. The significant differences in the efficacy and side effects between the two groups were analyzed. RESULTS: A total of 76 patients who completed follow-up were divided into CYP3A5 nonexpresser (CYP3A5*3/*3) group and CYP3A5 expresser (CYP3A5 *1/*3) group. The significant association between the CYP3A5 phenotype and TAC metabolism was observed. A total of 43 case-times patients exhibited adverse effects. The infection rate in CYP3A5 nonexpresser group (21.95%) was remarkably higher than the rate in CYP3A5 expresser group (5.71%). Blood concentration and C(0)/D levels were risk factors for adverse events through logistic regression analysis. There was no statistical difference between the study groups with respect to the efficacy. CONCLUSION: Our results demonstrated that CYP3A5 polymorphisms had important guiding roles in the treatment of IMN with tacrolimus. CYP3A5 expressers required higher daily doses of TAC to achieve the target drug concentration, but with fewer side effects. CYP3A5 genetic polymorphism might be used for TAC dosing adjustment to optimize the treatment for patients with IMN.
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spelling pubmed-71862132020-05-04 Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy Zhang, Chengning Duan, Suyan Guo, Miao Yuan, Yanggang Huang, Zhimin Zhu, Jingfeng Sun, Bin Zhang, Bo Xing, Changying Pharmgenomics Pers Med Original Research BACKGROUND: Tacrolimus (TAC) is beneficial for patients with idiopathic membranous nephropathy (IMN). It has a narrow therapeutic concentration range and many factors influence TAC blood concentration. CYP3A5 is the most important enzyme in TAC metabolism. The aim of this study was to analyze the effects of CYP3A5 gene polymorphisms on the efficacy and safety of TAC in IMN patients. PATIENTS AND METHODS: Patients with IMN who received oral TAC (0.05–0.075mg/kg/day) combined with prednisone (0.5mg/kg/day) from March 2016 to October 2018 were included. The data of clinical characteristics, therapeutic drugs and adverse reactions of patients were collected at baseline and during 24 weeks of treatment. Patients were divided into two groups according to different CYP3A5 genetic polymorphisms. The significant differences in the efficacy and side effects between the two groups were analyzed. RESULTS: A total of 76 patients who completed follow-up were divided into CYP3A5 nonexpresser (CYP3A5*3/*3) group and CYP3A5 expresser (CYP3A5 *1/*3) group. The significant association between the CYP3A5 phenotype and TAC metabolism was observed. A total of 43 case-times patients exhibited adverse effects. The infection rate in CYP3A5 nonexpresser group (21.95%) was remarkably higher than the rate in CYP3A5 expresser group (5.71%). Blood concentration and C(0)/D levels were risk factors for adverse events through logistic regression analysis. There was no statistical difference between the study groups with respect to the efficacy. CONCLUSION: Our results demonstrated that CYP3A5 polymorphisms had important guiding roles in the treatment of IMN with tacrolimus. CYP3A5 expressers required higher daily doses of TAC to achieve the target drug concentration, but with fewer side effects. CYP3A5 genetic polymorphism might be used for TAC dosing adjustment to optimize the treatment for patients with IMN. Dove 2020-04-23 /pmc/articles/PMC7186213/ /pubmed/32368128 http://dx.doi.org/10.2147/PGPM.S247892 Text en © 2020 Zhang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhang, Chengning
Duan, Suyan
Guo, Miao
Yuan, Yanggang
Huang, Zhimin
Zhu, Jingfeng
Sun, Bin
Zhang, Bo
Xing, Changying
Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy
title Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy
title_full Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy
title_fullStr Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy
title_full_unstemmed Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy
title_short Effects of CYP3A5 Polymorphisms on Efficacy and Safety of Tacrolimus Therapy in Patients with Idiopathic Membranous Nephropathy
title_sort effects of cyp3a5 polymorphisms on efficacy and safety of tacrolimus therapy in patients with idiopathic membranous nephropathy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186213/
https://www.ncbi.nlm.nih.gov/pubmed/32368128
http://dx.doi.org/10.2147/PGPM.S247892
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