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异基因造血干细胞移植受者持续输注期间CYP3A5基因多态性与他克莫司血药浓度变化的关系

Relationship between CYP3A5 Polymorphism and Tacrolimus Blood Concentration Changes in Allogeneic Hematopoietic Stem Cell Transplant Recipients during Continuous Infusion.

作者信息

Yoshikawa Naoki, Takeshima Hidemi, Sekine Masaaki, Akizuki Keiichi, Hidaka Tomonori, Shimoda Kazuya, Ikeda Ryuji

机构信息

Department of Pharmacy, University of Miyazaki Hospital, Miyazaki 889-1692, Japan.

Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.

出版信息

Pharmaceuticals (Basel). 2021 Apr 10;14(4):353. doi: 10.3390/ph14040353.

Abstract

A polymorphism in the gene encoding the metabolic enzyme cytochrome P450 family 3 subfamily A member 5 (CYP3A5) is a particularly influential factor in the use of tacrolimus in Japanese patients. Those who are homozygotic for the mutation lack CYP3A5 activity, which results in substantial individual differences in tacrolimus metabolism. The aim of this study was to analyze the relationship between individual differences in tacrolimus blood concentration changes and polymorphisms in allogeneic hematopoietic stem cell transplantation recipients during the period of increasing blood concentration of the drug following treatment onset. This was a prospective observational cohort study, involving 20 patients administered tacrolimus by continuous infusion. The subjects were divided into the and groups based on polymorphism analysis. The tacrolimus blood concentration/dose (C/D) ratio increased from day 1 and was largely stable on day 5, and a significant difference was observed between the and groups in the time course of the C/D ratio during this period ( < 0.05). This study reveals the effects of polymorphism on continuous changes in tacrolimus blood concentration.

摘要

编码代谢酶细胞色素P450 3A亚家族成员5(CYP3A5)的基因多态性是影响日本患者使用他克莫司的一个特别重要的因素。那些该基因突变的纯合子缺乏CYP3A5活性,这导致他克莫司代谢存在显著的个体差异。本研究的目的是分析在治疗开始后药物血药浓度上升期间,同种异体造血干细胞移植受者他克莫司血药浓度变化的个体差异与基因多态性之间的关系。这是一项前瞻性观察队列研究,纳入了20例通过持续输注给予他克莫司的患者。根据基因多态性分析将受试者分为两组。他克莫司血药浓度/剂量(C/D)比值从第1天开始升高,在第5天基本稳定,在此期间两组C/D比值的时间进程存在显著差异(P<0.05)。本研究揭示了基因多态性对他克莫司血药浓度持续变化的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2ac/8070336/1104a0ad6084/pharmaceuticals-14-00353-g001.jpg

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