成人患者体内伏立康唑代谢的影响因素分析

程林; 梁再明; 喻明洁; 孙凤军; 戴青

doi:10.6039/j.issn.1001-0408.2023.04.16

您当前的位置：

首页 >

文章列表页 >

成人患者体内伏立康唑代谢的影响因素分析

药物与临床 | 更新时间：2023-02-24

- 成人患者体内伏立康唑代谢的影响因素分析
- Analysis of influencing factors for the metabolism of voriconazole in adult patients
- 中国药房 2023年34卷第4期页码：466-470
- 作者机构：
  
  陆军军医大学第一附属医院药学部，重庆　400038
- 作者简介：
  
  副主任药师，硕士。研究方向：抗感染药物的治疗药物监测。电话：023-68766797。E-mail：cheng7zhu@163.com
  副主任药师。研究方向：药物分析。电话：023-68766797。E-mail：dq050@163.com
- 基金信息：
  
  重庆市科卫联合医学科研项目(2021MSXM218)
- DOI：10.6039/j.issn.1001-0408.2023.04.16
  中图分类号： R969.1;R969.3
- 纸质出版日期：2023-02-28，
  
  收稿日期：2022-07-27，
  
  修回日期：2023-01-06，
扫描看全文
程林,梁再明,喻明洁等.成人患者体内伏立康唑代谢的影响因素分析 ^Δ[J].中国药房,2023,34(04):466-470.

CHENG Lin,LIANG Zaiming,YU Mingjie,et al.Analysis of influencing factors for the metabolism of voriconazole in adult patients[J].ZHONGGUO YAOFANG,2023,34(04):466-470.
程林,梁再明,喻明洁等.成人患者体内伏立康唑代谢的影响因素分析 ^Δ[J].中国药房,2023,34(04):466-470. DOI： 10.6039/j.issn.1001-0408.2023.04.16.

CHENG Lin,LIANG Zaiming,YU Mingjie,et al.Analysis of influencing factors for the metabolism of voriconazole in adult patients[J].ZHONGGUO YAOFANG,2023,34(04):466-470. DOI： 10.6039/j.issn.1001-0408.2023.04.16.

摘要

目的

分析影响成人患者体内伏立康唑代谢的因素，为伏立康唑的临床合理应用提供参考。

方法

回顾性分析2021年4月－2022年3月我院使用伏立康唑并进行治疗药物监测的103例成人患者资料，同时测定血浆伏立康唑谷浓度（

）、伏立康唑氮氧化物浓度（

），并计算

值；采用Pearson’s相关性分析影响伏立康唑

、

值的因素；采用多元线性回归模型分析伏立康唑

、

值的独立影响因素。

结果

患者基础疾病以肺炎、肾脏疾病和白血病为主；感染真菌中以曲霉菌、念珠菌和酵母样真菌为主；给药方式主要为静脉滴注，以联用质子泵抑制剂患者最多。C反应蛋白（CRP）、总胆红素（TBIL）、直接胆红素（DBIL）、间接胆红素（IBIL）水平与伏立康唑

均呈正相关，血小板计数和白蛋白水平与伏立康唑

均呈负相关；CRP、TBIL、DBIL水平与

值均呈正相关，白蛋白水平与

值呈负相关。多元线性回归模型分析结果显示，伏立康唑

的独立影响因素有CRP、IBIL、伏立康唑给药方式和给药剂量，伏立康唑

的独立影响因素有CRP、DBIL和年龄。

结论

CRP、IBIL、伏立康唑给药方式和给药剂量是影响伏立康唑

的独立因素，CRP、DBIL和年龄是影响

值的独立因素；临床使用伏立康唑时，应考虑上述指标对伏立康唑代谢的影响，合理调整伏立康唑的给药方式和剂量。

Abstract

OBJECTIVE

To analyze the influencing factors for the metabolism of voriconazole in adult patients， and to provide reference for the rational use of voriconazole in clinic.

METHODS

The clinical data of adult patients admitted in our hospital receiving voriconazole and therapeutic drug monitoring from April 2021 to March 2022 were collected. The trough concentration of voriconazole （

） and plasma concentration of voriconazole-

-oxide concentration （

） were determined， and voriconazole-to-voriconazole

-oxide concentration ratio （

） was calculated. Pearson’s correlation analysis was used to analyze the influencing factors for

and

of voriconazole. Multiple linear regression models were used to analyze the independent influencing factors for

and

of voriconazole.

RESULTS

The underlying diseases of the patients were mainly pneumonia， kidney disease and leukemia. The detected fungi were mainly

Aspergillus

，

Candida

and yeast-like fungi. Voriconazole was mainly administered by intravenous drip， especially in patients who used proton pump inhibitor in combination. The levels of C-reactive protein （CRP）， total bilirubin （TBIL）， direct bilirubin （DBIL） and indirect bilirubin （IBIL） were positively correlated with

of voriconazole， while platelet count and albumin levels were negatively correlated with voriconazole

. The levels of CRP， TBIL and DBIL were positively correlated with

， while albumin levels were negatively correlated with

. Multiple linear regression analysis showed that the independent influencing factors of voriconazole

included the levels of CRP and IBIL， route of administration and dose of voriconazole， and the independent influencing factors of voriconazole

were the levels of CRP and DBIL and age.

CONCLUSIONS

The levels of CRP and IBIL， route of administration and dose of voriconazole are independent influencing factors of voriconazole

； the levels of CRP and DBIL and age are independent influencing factors of voriconazole

. The influence of above indexes on the metabolism of voriconazole should be considered when using voriconazole clinically； and the route of administration and dose of voriconazole should be adjusted reasonably.

关键词

伏立康唑伏立康唑氮氧化物治疗药物监测谷浓度影响因素相关性

Keywords

voriconazole-N-oxidetherapeutic drug monitoringtrough concentrationinfluencing factorcorrelation

references

ULLMANN A J，AGUADO J M，ARIKAN-AKDAGLI S，et al. Diagnosis and management of Aspergillus diseases：executive summary of the 2017 ESCMID-ECMM-ERS guideline[J]. Clin Microbiol Infect，2018，24（Suppl 1）：e1-e38.

HYLAND R，JONES B C，SMITH D A. Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole[J]. Drug Metab Dispos，2003，31（5）：540-547.

THEURETZBACHER U，IHLE F，DERENDORF H. Pharmacokinetic/pharmacodynamic profile of voricona-zole[J]. Clin Pharmacokinet，2006，45（7）：649-663.

PURKINS L，WOOD N，GHAHRAMANI P，et al. Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens[J]. Antimicrob Agents Chemother，2002，46（8）：2546-2553.

CHEN K，ZHANG X L，KE X Y，et al. Individualized medication of voriconazole：a practice guideline of the division of therapeutic drug monitoring，Chinese pharmaco-logical society[J]. Ther Drug Monit，2018，40（6）：663-674.

NIIOKA T，FUJISHIMA N，ABUMIYA M，et al. Relationship between the CYP2C19 phenotype using the voriconazole-to-voriconazole N-oxide plasma concentration ratio and demographic and clinical characteristics of Japanese patients with different CYP2C19 genotypes[J]. Ther Drug Monit，2017，39（5）：514-521.

VERINGA A，TER AVEST M，SPAN L F，et al. Voricona-zole metabolism is influenced by severe inflammation：a prospective study[J]. J Antimicrob Chemother，2017，72（1）：261-267.

VANSTRAELEN K，WAUTERS J，VERCAMMEN I，et al. Impact of hypoalbuminemia on voriconazole pharmacokinetics in critically ill adult patients[J]. Antimicrob Agents Chemother，2014，58（11）：6782-6789.

GEIST M J，EGERER G，BURHENNE J，et al. Steady-state pharmacokinetics and metabolism of voriconazole in patients[J]. J Antimicrob Chemother，2013，68（11）：2592-2599.

ZHAO Y C，LIN X B，ZHANG B K，et al. Predictors of adverse events and determinants of the voriconazole trough concentration in kidney transplantation recipients[J]. Clin Transl Sci，2021，14（2）：702-711.

TANG D，YAN M，SONG B L，et al. Population pharmacokinetics，safety and dosing optimization of voriconazole in patients with liver dysfunction：a prospective observational study[J]. Br J Clin Pharmacol，2021，87（4）：1890-1902.

YASU T，KONUMA T，KURODA S，et al. Effect of cumulative intravenous voriconazole dose on renal function in hematological patients[J]. Antimicrob Agents Chemother，2018，62（9）：e00507-e00518.

VREUGDENHIL B，VAN DER VELDEN W J F M，FEUTH T，et al. Moderate correlation between systemic IL-6 responses and CRP with trough concentrations of voriconazole[J]. Br J Clin Pharmacol，2018，84（9）：1980-1988.

GAUTIER-VEYRET E，TRUFFOT A，BAILLY S，et al. Inflammation is a potential risk factor of voriconazole overdose in hematological patients[J]. Fundam Clin Pharmacol，2019，33（2）：232-238.

VAN WANROOY M J，SPAN L F，RODGERS M G，et al. Inflammation is associated with voriconazole trough concentrations[J]. Antimicrob Agents Chemother，2014，58（12）：7098-7101.

向荣凤，尚圣兰，熊丽蓉，等. 液相色谱-串联质谱法测定人血浆中伏立康唑和伏立康唑氮氧化物浓度及其临床应用[J]. 第三军医大学学报，2019，41（15）：1478-1484.

程林，翁邦碧，向荣凤，等. 老年肺部侵袭性真菌感染患者伏立康唑谷浓度与肝功能损伤的关系[J]. 第三军医大学学报，2020，42（19）：1944-1949.

戴婷婷，胡林，李逃明，等. 伏立康唑所致精神异常与其血浆谷浓度的相关性探讨[J]. 中国药学杂志，2018，53（5）：375-378.

CHAN S Y，HUGHES R M，WOO K，et al. Reasons for voriconazole prophylaxis discontinuation in allogeneic hematopoietic cell transplant recipients：a real-life paradigm[J]. Med Mycol，2020，58（8）：1029-1036.

CHENG L，XIANG R F，LIU F，et al. Therapeutic drug monitoring and safety of voriconazole in elderly patients[J]. Int Immunopharmacol，2020，78：106078.

WU K C，LIN C J. The regulation of drug-metabolizing enzymes and membrane transporters by inflammation：evidences in inflammatory diseases and age-related disorders[J]. J Food Drug Anal，2019，27（1）：48-59.

CHANTHARIT P，TANTASAWAT M，KASAI H，et al. Population pharmacokinetics of voriconazole in patients with invasive aspergillosis：serum albumin level as a novel marker for clearance and dosage optimization[J]. Ther Drug Monit，2020，42（6）：872-879.

ZHAO Y C，XIAO C L，HOU J J，et al. A large sample re-trospective study on the distinction of voriconazole concentration in Asian patients from different clinical departments[J]. Pharmaceuticals（Basel），2021，14（12）：1239.

BLANCO DORADO S，MAROÑAS AMIGO O，LATORRE-PELLICER A，et al. A multicentre prospective study evaluating the impact of proton-pump inhibitors omeprazole and pantoprazole on voriconazole plasma concentrations[J]. Br J ClinPharmacol，2020，86（8）：1661-1666.

ALLEGRA S，DE FRANCIA S，DE NICOLÒ A，et al. Effect of gender and age on voriconazole trough concentra-tions in Italian adult patients[J]. Eur J Drug Metab Pharmacokinet，2020，45（3）：405-412.

BOLCATO L，KHOURI C，VERINGA A，et al. Combined impact of inflammation and pharmacogenomic variants on voriconazole trough concentrations：a meta-analysis of individual data[J]. J Clin Med，2021，10（10）：2089.

SHANGS L，CHENGL，LIX Y，et al. Effect of CYP2C19 polymorphism on the plasma voriconazole concentration and voriconazole-to-voriconazole-N-oxide concentration ratio in elderly patients[J]. Mycoses，2020，63（11）：1181-1190

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

基因多态性对含奥沙利铂化疗方案治疗Ⅲ、Ⅳ期结直肠癌疗效及毒副作用的影响

我院2008－2012年抗菌药物使用量与革兰阴性菌耐药性分析

天津市各级医疗机构输液相关不良事件与滴注速度相关性分析

紫锥菊的形态学性状、分布高度与质量相关性研究Δ

头孢曲松致免疫性溶血的文献分析