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CYP2C19基因多态性对异基因造血干细胞移植后血液病患者伏立康唑不良反应发生情况的影响

Influence of CYP2C19 Genotypes on the Occurrence of Adverse Drug Reactions of Voriconazole among Hematological Patients after Allo-HSCT.

作者信息

Sienkiewicz Beata, Urbaniak-Kujda Donata, Dybko Jarosław, Dryś Andrzej, Hurkacz Magdalena, Wróbel Tomasz, Wiela-Hojeńska Anna

机构信息

Department of Clinical Pharmacology, Faculty of Pharmacy, Wrocław Medical University, 211a Borowska St, 50-556, Wrocław, Poland.

Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wrocław Medical University, 4 Wybrzeże Pasteura St, 50-367, Wrocław, Poland.

出版信息

Pathol Oncol Res. 2018 Jul;24(3):541-545. doi: 10.1007/s12253-017-0264-9. Epub 2017 Jul 6.

Abstract

The aim of this study was to determine the influence of different CYP2C19 genotypes on selected liver function parameters, and ADR occurrence during VCZ prophylaxis in adult patients after allo-HSCT (allogeneic hematopoietic stem cell transplantation). CYP2C19 mutations were determined in a cohort of 30 adults using PCR-RFLP methods established by Sim et al. and Goldstein and Blaisdell. The patients' protocol included biometrical and biochemical data, information on the underlying disease, chemotherapy, molds infections occurring during VCZ treatment, adverse drug reactions typical for the use of voriconazole, and probable drug - drug interactions. The observation and reporting of ADR took place from the -1 until the +20th day of VCZ therapy. For statistical analysis the χ2 test was used (p < 0.05). Among the examined patients 23 suffered from at least one side effect during VCZ therapy. Most frequent ADR were gastrointestinal disturbances (n = 15), nervous system (n = 11) and skin (n = 7) disorders. Patients with at least one loss of function allele (*2) were more likely to experience adverse drug reactions than those, with different genotypes. Due to the limited number of patients the result could not be proven with a statistical significance. Previous determination of CYP2C19 genotype may be a useful tool for prevention of adverse drug reactions during VCZ prophylaxis among patients after allo-HSCT.

摘要

本研究的目的是确定不同的CYP2C19基因型对异基因造血干细胞移植(allo-HSCT)后成年患者伏立康唑(VCZ)预防期间选定的肝功能参数及药物不良反应(ADR)发生情况的影响。采用Sim等人以及Goldstein和Blaisdell建立的聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,对30名成年患者的队列进行CYP2C19突变检测。患者方案包括生物统计学和生化数据、基础疾病信息、化疗情况、VCZ治疗期间发生的霉菌感染、伏立康唑使用典型的药物不良反应以及可能的药物-药物相互作用。ADR的观察和报告在VCZ治疗的第-1天至第+20天进行。统计分析采用χ2检验(p < 0.05)。在接受检查的患者中,23名在VCZ治疗期间至少出现一种副作用。最常见的ADR是胃肠道紊乱(n = 15)、神经系统(n = 11)和皮肤(n = 7)疾病。与具有不同基因型的患者相比,至少有一个功能缺失等位基因(*2)的患者更有可能发生药物不良反应。由于患者数量有限,结果未能得到统计学显著性验证。预先确定CYP2C19基因型可能是预防allo-HSCT后患者VCZ预防期间药物不良反应的有用工具。

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