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学科主题: 药学
题名:
Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections
作者: Wang, Taotao1; Zhu, Huifang2; Sun, Jinyao1; Cheng, Xiaoliang1,3; Xie, Jiao1; Dong, Haiyan1; Chen, Limei4; Wang, Xue5; Xing, Jianfeng6; Dong, Yalin1
关键词: Voriconazole ; Efficacy ; Safety ; Hepatotoxicity ; CYP2C19 ; Trough plasma concentrations
刊名: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
发表日期: 2014-11-01
DOI: 10.1016/j.ijantimicag.2014.07.013
卷: 44, 期:5, 页:436-442
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
研究领域[WOS]: Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy
关键词[WOS]: INTRAVENOUS VORICONAZOLE ; ANTIFUNGAL AGENT ; PHARMACOKINETICS ; MULTICENTER ; IDENTIFICATION ; GENOTYPE ; TRIAZOLE
英文摘要:

The aim of this study was to determine an optimum voriconazole target concentration, to study the influence of CYP2C19 gene status on metabolism of voriconazole and to identify a dose-adjustment strategy for voriconazole according to CYP2C19 polymorphism in patients with invasive fungal infections. A total of 328 voriconazole trough plasma concentrations (C-min) were collected and monitored from 144 patients. Information on efficacy and safety was obtained. Voriconazole therapy was effective in 81.9% of patients (118/144), and 12.5% (18/144) exhibited signs of hepatotoxicity. The relationships between voriconazole C-min and clinical response and hepatotoxicity were explored using logistic regression, and a target clinical C-min range of 1.5-4 mg/L was identified. Values of voriconazole C-min and the ratio of C-min to concentration of voriconazole-N-oxide ( Cmin/CN) of poor metabolisers (PMs) were significantly higher than extensive metabolisers and intermediate metabolisers. Model-based simulations showed that PM patients could be safely and effectively treated with 200 mg twice daily orally or intravenously, and non-PM patients with 300 mg twice daily orally or 200 mg twice daily intravenously. This study highlighted that voriconazole C-min and C-min/C-N are strongly influenced by CYP2C19 polymorphism, and gene-adjusted dosing is important to achieve therapeutic levels that maximise therapeutic response and minimise hepatotoxicity. (C) 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

语种: 英语
所属项目编号: 30973673 ; 81201490
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000344938800010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52529
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Tengzhou Cent Peoples Hosp, Dept Pharm, Tengzhou 277500, Peoples R China
2.Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Dept Pharm, Xian 710061, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100871, Peoples R China
4.Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Dept Hematol, Xian 710061, Peoples R China
5.Xi An Jiao Tong Univ, Affiliated Hosp 1, Coll Med, Cent Intens Care Unit, Xian 710061, Peoples R China
6.Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, Xian 710061, Peoples R China

Recommended Citation:
Wang, Taotao,Zhu, Huifang,Sun, Jinyao,et al. Efficacy and safety of voriconazole and CYP2C19 polymorphism for optimised dosage regimens in patients with invasive fungal infections[J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,2014,44(5):436-442.
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