Voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration

Lin CHENG; Bangbi WENG; Rongfeng XIANG; Peiyuan XIA

doi:10.16016/j.1000-5404.202003031

您当前的位置：

首页 >

文章列表页 >

Voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration

Clinical Medicine | 更新时间：2026-01-09

- Voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration
- Journal of Third Military Medical University Vol. 42, Issue 13, Pages: 1350-1354(2020)
- 作者机构：
  
  400038 重庆, 陆军军医大学(第三军医大学)第一附属医院药学部
- 作者简介：
- 基金信息：
  
  the Promotion Plan for Military Medical Innovation Capacity of the First Affiliated Hospital of Army Medical University(SWH2019QNLC-05)
- DOI：10.16016/j.1000-5404.202003031
  CLC： R591.1;R969.3;R978.5
- Received：04 March 2020，
  
  Revised：2020-03-25，
  
  Published：15 July 2020
- 稿件说明：
移动端阅览
Lin CHENG, Bangbi WENG, Rongfeng XIANG, et al. Voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration[J]. Journal of Third Military Medical University, 2020, 42(13): 1350-1354.
DOI：

Lin CHENG, Bangbi WENG, Rongfeng XIANG, et al. Voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration[J]. Journal of Third Military Medical University, 2020, 42(13): 1350-1354. DOI： 10.16016/j.1000-5404.202003031.

摘要

目的

探讨肺部侵袭性真菌感染患者中伏立康唑所致低血钾和低血钠的发生情况及其与伏立康唑谷浓度的相关性。

方法

对2017年10月8日至2019年4月30日我院收治的进行伏立康唑治疗药物监测患者的临床资料进行回顾性分析。收集患者的性别、年龄、体质量、基础疾病、真菌感染类型、给药方式、给药剂量、伏立康唑谷浓度、血钾浓度、血钠浓度、给药后出现低血钾和低血钠的时间。对伏立康唑谷浓度与血钾、血钠浓度的相关性进行Pearson相关性分析。

结果

共纳入142例肺部侵袭性真菌感染患者

267个伏立康唑谷浓度。患者以男性为主(64.1%); 基础疾病以白血病(26.8%)和高血压(32.4%)为主

其次为糖尿病、慢性阻塞性肺疾病、肾移植和冠状动脉粥样硬化性心脏病; 感染真菌以曲霉菌为主(40.8%)。伏立康唑谷浓度为2.9(1.6

4.9)μg/mL

范围0.4~15.5 μg/mL。共42例患者出现低血钾

占29.6%;21例患者出现低血钠

占14.8%。伏立康唑使用后1~5 d出现低血钾和低血钠的比例最高

分别占57.1%和42.9%。出现低血钾和低血钠患者的给药方式均以静脉滴注为主。口服伏立康唑后出现低血钾的时间长

静脉滴注伏立康唑后出现低血钾的时间短。患者血钾和血钠与伏立康唑谷浓度不存在相关性(

=0.001

=0.989;

=0.150

=0.052)。

结论

在常规治疗剂量下

静脉滴注伏立康唑引起低血钾和低血钠的比例较高

且多发生于伏立康唑使用后早期

临床应用中应注意此不良反应。

Abstract

Objective

To investigate the incidence rates of voriconazole-induced hypokalemia and hyponatremia and their correlations with voriconazole trough concentration in the patients with lung invasive aspergillosis.

Methods

The clinical data of the patients receiving therapeutic drug monitoring for voriconazole due to lung invasive aspergillosis in our hospital from 8 October

2017 to 30 April

2019 were collected and retrospectively analyzed. Sex

age

body weight

baseline diseases

types of fungal infection

route of administration

daily voriconazole dose

voriconazole trough concentration

serum potassium and sodium concentrations

and the times of hypokalemia and hyponatremia after administration were collected in all the patients. The relationships of voriconazole trough concentration with serum potassium and sodium concentrations were analyzed with Pearson's correlation analysis.

Results

A total of 142 patients with lung invasive aspergillosis were enrolled

with 267 voriconazole trough concentrations. The patients were mainly men (64.1%). Their mainly baseline diseases were majorly leukaemia (26.8%) and hypertension (32.4%)

followed by diabetes mellitus

chronic obstructive pulmonary disease

kidney transplantation

and coronary atherosclerotic heart disease. The most common infected fungus was Aspergillus (40.8%). The voriconazole trough concentration was 2.9 (1.6

4.9) μg/mL

with a range of 0.4~15.5 μg/mL among the patients

42 patients suffered from hypokalemia

accounting for 29.6%

and 21 patients suffered from hyponatremia

accounting for 14.8%. Hypokalemia and hyponatremia were mainly observed in 1 to 5 d after voriconazole administration

accounting for 57.1% and 42.9%

respectively. Most of the patients with hypokalemia and hyponatremia received the agent through intravenous injection. The duration of hypokalemia after oral administration was long

while the time with intravenous injection was short. There were no correlations of voriconazole trough concentration with serum potassium and sodium (

=0.001

=0.989;

=0.150

=0.052).

Conclusion

Under routine dose

the incidences of hypokalemia and hyponatremia are quite high after intravenous injection of voriconazole

and they mainly occur in the early time after administration. Special attention should be paid to the adverse effects in clinical practice.

关键词

Keywords

references

OREN I, PAUL M. Up to date epidemiology, diagnosis and management of invasive fungal infections[J]. Clin Microbiol Infect, 2014, 20(Suppl 6): 1-4. DOI:10.1111/1469-0691.12642.

张静, 何礼贤.侵袭性肺真菌病诊治指南解读[J].中国药物应用与监测, 2011, 8(5): 261-265. DOI:10.3969/j.issn.1672-8157.2011.05.001.

ZHANG J, HE L X. Interpretation of guidelines for invasive pulmonary fungal disease[J]. Chin J Drug Appl Monit, 2011, 8(5): 261-265. DOI:10.3969/j.issn.1672-8157.2011.05.001.

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. DOI:10.1016/j.cmi.2018.01.002.

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 Pharmacological Society[J ] . Ther Drug Monit, 2018, 40(6): 663-674. DOI:10.1097/FTD.0000000000000561.

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. DOI:10.1016/j.intimp.2019.106078.

HASHEMIZADEH Z, BADIEE P, MALEKHOSEINI S A, et al . Observational study of associations between voriconazole therapeutic drug monitoring, toxicity, and outcome in liver transplant patients[J ] . Antimicrob Agents Chemother, 2017, 61(12): e01211-e01217. DOI:10.1128/AAC.01211-17.

BENITEZ L L, CARVER P L. Adverse effects associated with long-term administration of azole antifungal agents[J]. Drugs, 2019, 79(8): 833-853. DOI:10.1007/s40265-019-01127-8.

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. DOI:10.16016/j.1000-5404.201902067.

XIANGR F, SHANG S L, XIONG L R, et al . Determination of voriconazole and its N-oxide in human plasma by LC-MS/MS and its clinical application[J ] . J Third Mil Med Univ, 2019, 41(15): 1478-1484. DOI:10.16016/j.1000-5404.201902067.

SATOH T, TOMIKAWA Y, TAKANASHI K, et al . Studies on the interactions between drugs and estrogen. III. Inhibitory effects of 29 drugs reported to induce gynecomastia on the glucuronidation of estradiol[J ] . Biol Pharm Bull, 2004, 27(11): 1844-1849. DOI:10.1248/bpb.27.1844.

SATOH T, ITOH S, SEKI T, et al . On the inhibitory action of 29 drugs having side effect gynecomastia on estrogen production[J ] . J Steroid Biochem Mol Biol, 2002, 82(2/3): 209-216. DOI:10.1016/s0960-0760(02)00154-1.

SAAD A H, DEPESTEL D D, CARVER P L. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants[J]. Pharmacotherapy, 2006, 26(12): 1730-1744. DOI:10.1592/phco.26.12.1730.

刘学松, 何为群, 陈文英, 等.肺部真菌感染患者伏立康唑血药浓度监测的临床应用[J].国际呼吸杂志, 2016, 36(20):1521-1526.DOI:10.3760/cma.j.issn.1673-436X.2016.20.001.

LIU X S, HE W Q, CHEN W Y, et al . Monitor the voriconazole trough concentration of patients with pulmonary fungal infection in clinical application[J ] . Int J Respir, 2016, 36(20):1521-1526. DOI:10.3760/cma.j.issn.1673-436X.2016.20.001.

武琳琳, 江嘉义, 王晗晗, 等.伏立康唑治疗血液病合并侵袭性真菌病的疗效及安全性观察[J].安徽医学, 2019, 40(6): 664-667.

WU L L, JIANG J Y, WANG H H, et al . Efficacy and safety of voriconazole in the treatment of hematopathy with invasive mycosis [J ] . Anhui Med J, 2019, 40(6): 664-667.

FILIPPATOS T D, MAKRI A, ELISAF M S, et al . Hyponatremia in the elderly: challenges and solutions[J ] . Clin Interv Aging, 2017, 12: 1957-1965. DOI:10.2147/CIA.S138535.

MATTHAIOU D K, DIMOPOULOS G, TACCONE F S, et al . Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort[J ] . Med Mycol, 2018, 56(6): 668-678. DOI:10.1093/mmy/myx117.

LIANG S Y. Sepsis and other infectious disease emergencies in the elderly[J]. Emerg Med Clin North Am, 2016, 34(3): 501-522. DOI:10.1016/j.emc.2016.04.005.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Relationship between voriconazole trough concentration and liver injury in elderly patients with lung invasive aspergillosis

Determination of voriconazole and its N-oxide in human plasma by LC-MS/MS and its clinical application

Related Author

程林

翁邦碧

向荣凤

孙凤军

向荣凤

尚圣兰

熊丽蓉

喻明洁

Related Institution

No data

⁰