Combined impact of hypoalbuminemia and pharmacogenomic variants on voriconazole trough concentration: data from a real-life clinical setting in the Chinese population.

IF 1.9 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2024-05-01 Epub Date: 2023-08-20 DOI:10.1080/1120009X.2023.2247208

Yuanyuan Li, Ying Zhang, Jinxia Zhao, Jialu Bian, Yinyu Zhao, Xu Hao, Boyu Liu, Lei Hu, Fang Liu, Changqing Yang, Yufei Feng, Lin Huang

{"title":"Combined impact of hypoalbuminemia and pharmacogenomic variants on voriconazole trough concentration: data from a real-life clinical setting in the Chinese population.","authors":"Yuanyuan Li, Ying Zhang, Jinxia Zhao, Jialu Bian, Yinyu Zhao, Xu Hao, Boyu Liu, Lei Hu, Fang Liu, Changqing Yang, Yufei Feng, Lin Huang","doi":"10.1080/1120009X.2023.2247208","DOIUrl":null,"url":null,"abstract":"Voriconazole (VRC) displays highly variable pharmacokinetics impacting treatment efficacy and safety. To provide evidence for optimizing VRC therapy regimens, the authors set out to determine the factors impacting VRC steady-state trough concentration (Cmin) in patients with various albumin (Alb) level. A total of 275 blood samples of 120 patients and their clinical characteristics and genotypes of CYP2C19, CYP3A4, CYP3A5, CYP2C9, FMO3, ABCB1, POR, NR1I2 and NR1I3 were included in this study. Results of multivariate linear regression analysis demonstrated that C-reactive protein (CRP) and total bilirubin (T-Bil) were predictors of the VRC Cmin adjusted for dose in patients with hypoalbuminemia (Alb < 35 g/L) (R2 = 0.16, P < 0.001). Additionally, in patients with normal albumin level (Alb ≥ 35 g/L), it resulted in a significant model containing factors of the poor metabolizer (PM) CYP2C19 genotype and CRP level (R2 = 0.26, P < 0.001). Therefore, CRP and T-Bil levels ought to receive greater consideration than genetic factors in patients with hypoalbuminemia.","PeriodicalId":15338,"journal":{"name":"Journal of Chemotherapy","volume":" ","pages":"179-189"},"PeriodicalIF":1.9000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1120009X.2023.2247208","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/20 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}

引用次数: 0

Abstract

Voriconazole (VRC) displays highly variable pharmacokinetics impacting treatment efficacy and safety. To provide evidence for optimizing VRC therapy regimens, the authors set out to determine the factors impacting VRC steady-state trough concentration (C_min) in patients with various albumin (Alb) level. A total of 275 blood samples of 120 patients and their clinical characteristics and genotypes of CYP2C19, CYP3A4, CYP3A5, CYP2C9, FMO3, ABCB1, POR, NR1I2 and NR1I3 were included in this study. Results of multivariate linear regression analysis demonstrated that C-reactive protein (CRP) and total bilirubin (T-Bil) were predictors of the VRC C_min adjusted for dose in patients with hypoalbuminemia (Alb < 35 g/L) (R² = 0.16, P < 0.001). Additionally, in patients with normal albumin level (Alb ≥ 35 g/L), it resulted in a significant model containing factors of the poor metabolizer (PM) CYP2C19 genotype and CRP level (R² = 0.26, P < 0.001). Therefore, CRP and T-Bil levels ought to receive greater consideration than genetic factors in patients with hypoalbuminemia.

查看原文本刊更多论文

低白蛋白血症和药物基因组变异对伏立康唑谷浓度的综合影响：来自中国人群真实临床环境的数据。

伏立康唑（VRC）的药代动力学变化很大，对治疗效果和安全性都有影响。为了为优化伏立康唑治疗方案提供证据，作者着手确定影响不同白蛋白（Alb）水平患者的伏立康唑稳态谷浓度（Cmin）的因素。本研究共纳入了 120 例患者的 275 份血样，以及他们的临床特征和 CYP2C19、CYP3A4、CYP3A5、CYP2C9、FMO3、ABCB1、POR、NR1I2 和 NR1I3 的基因型。多变量线性回归分析结果表明，C反应蛋白（CRP）和总胆红素（T-Bil）是低白蛋白血症（Alb < 35 g/L）患者剂量调整后 VRC Cmin 的预测因子（R2 = 0.16，P CYP2C19 基因型和 CRP 水平（R2 = 0.26，P

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

期刊介绍： The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.