1.广西医科大学第一附属医院药学部,南宁 530021
2.广西医科大学药学院,南宁 530021
Received:28 December 2022,
Revised:2023-03-20,
Accepted:05 May 2023,
Published:28 June 2023
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王希斌,刘滔滔,程道海,等.成人伏立康唑个体化用药监测分析[J].重庆医科大学学报,2023,48(6):721-725.
Wang Xibin,Liu Taotao,Cheng Daohai,et al.Individualized medication monitoring of voriconazole in adults[J].Journal of Chongqing Medical University,2023,48(6):721-725.
王希斌,刘滔滔,程道海,等.成人伏立康唑个体化用药监测分析[J].重庆医科大学学报,2023,48(6):721-725. DOI: 10.13406/j.cnki.cyxb.003258.
Wang Xibin,Liu Taotao,Cheng Daohai,et al.Individualized medication monitoring of voriconazole in adults[J].Journal of Chongqing Medical University,2023,48(6):721-725. DOI: 10.13406/j.cnki.cyxb.003258.
目的
2
基于《伏立康唑个体化用药指南》中伏立康唑的谷浓度与抗感染的疗效、肝脏毒性相关性仅以一个中等质量的证据来评判,不能很好满足临床需求。本论文将建立动态监测成人住院患者的伏立康唑谷浓度变化,力求探究谷浓度与疗效、不良反应的相关性。
方法
2
收集使用伏立康唑治疗的成人患者63例,共107份血液标本,采用酶免方法动态监测伏立康唑的药物谷浓度,观察患者的用药疗效、有无不良反应,剖析伏立康唑谷浓度与临床指标的相关性。
结果
2
①使用常规剂量伏立康唑治疗后,62/107(57.9%)血液标本的伏立康唑谷浓度在0.5~5.0 μg/mL,均数为2.7 μg/mL;4/107(3.7%)血液标本的谷浓度
<
0.5 μg/mL,均数为0.3 μg/mL;41/107(38.4%)血液标本的谷浓度
>
5.0 μg/mL,中位数为8.7 μg/mL。②谷浓度
<
0.5 μg/mL组、谷浓度≥0.5 μg/mL组治疗有效的比率分别为50.0%、74.5%,但2组差异无统计学意义(
P
=0.624)。提高1例谷浓度
<
0.5 μg/mL且治疗无效的患者剂量,使谷浓度达到有效浓度,感染症状获得改善。③10例(15.8%)发生不良反应,谷浓度
>
5.0 μg/mL的患者与谷浓度≤5.0 μg/mL的患者不良反应发生率分别为18.2%、14.6%,主要体现为肝功能异常。④伏立康唑谷浓度≤5.0 μg/mL的患者组与谷浓度
>
5.0 μg/mL的患者组碱性磷酸酶(alkaline phosphatase,ALP)、谷氨酰转肽酶(glutamyl transpeptidase,GGT)差异有统计学意义(
P
<
0.05),当谷浓度
>
5.0 μg/mL时,抗感染治疗后,降钙素原(procalcitonin,PCT)明显降低(
P<
0.05)。
结论
2
伏立康唑血药浓度个体间差异较大,必须规律监测谷浓度。伏立康唑谷浓度与肝功能、感染指标相关,可能要加大人群数或者在CYP2C19基因检测支持下来观察谷浓度与疗效、不良反应的相关性。
Objective
2
According to the trough concentration,anti-infective efficacy,and hepatotoxicity of voriconazole in Individualized Medication of Voriconazole:A Practice Guideline of the Division of Therapeutic Drug Monitoring, the judgment based on medium-quality evidence cannot meet clinical needs. This article will perform dynamic monitoring of the trough concentration of voriconazole in adult inpatients to investigate the association of trough concentration with therapeutic efficacy and adverse reactions.
Methods
2
A total of 107 blood samples were collected from 63 adult patients who were treated with voriconazole, and enzyme immunoassay was used for dynamic monitoring of the trough concentration of voriconazole. The patients were observed in terms of treatment outcome and adverse reactions,and the correlation of the trough concentration of voriconazole with clinical indices was analyzed.
Results
2
After treatment with voriconazole at the conventional dose,the trough concentration of voriconazole was 0.5-5.0 μg/mL in 57.9%(62/107) of the samples,with a averge concentration of 2.7 μg/mL;the trough concentration of voriconazole was
<
0.5 μg/mL in 3.7%(4/107) of the samples,with a averge concentration of 0.3 μg/mL;the trough concentration of voriconazole was
>
5.0 μg/mL in 38.4% (41/107) of the samples,with a median concentration of 8.7 μg/mL. The patients with a trough concentration of
<
0.5 μg/mL had a response rate of 50.0%,while those with a trough concentration of ≥0.5 μg/mL had a response rate of 74.5%,and there was no significant difference between the two groups(
P
=0.624). The dose was increased for one patient who had a trough concentration of
<
0.5 μg/mL and had no response to treatment,and the symptoms of infection were improved after effective trough concentration was reached. Adverse reactions were observed in 10 patients(15.8%), and the incidence rate of adverse reactions was 18.2% in patients with a trough concentration of
>
5.0 μg/mL and 14.6% in those with a trough concentration of ≤5.0 μg/mL, with the main adverse reaction of abnormal liver function. There were significant differences in alkaline phosphatase and gamma-glutamyl transpeptidase between the patients with a trough concentration of
>
5.0 μg/mL and those with a trough concentration of ≤5.0 μg/mL(
P
<
0.05),and when the trough concentration of voriconazole was
>
5.0 μg/mL,there was a significant reduction in procalcitonin after anti-infective therapy(
P
<
0.05).
Conclusion
2
There is a large difference in the plasma concentration of voriconazole between individuals, and its trough concentration must be monitored regularly. The trough concentration of voriconazole is associated with liver function parameters and infection indicators, and it may be necessary to increase sample size or perform CYP2C19 genetic testing to observe the association of trough concentration with therapeutic efficacy and adverse reactions.
刘思敏 , 蔡 俊 , 李慧馨 , 等 . 成人应用伏立康唑的群体药动学研究进展 [J ] . 中国临床药理学与治疗学 , 2019 , 24 ( 9 ): 1015 - 1023 .
Liu SM , Cai J , Li HX , et al . Research progress in population pharmacokinetics of voriconazole in adults [J ] . Chin J Clin Pharmacol Ther , 2019 , 24 ( 9 ): 1015 - 1023 .
陈 旭 , 何 仁 , 杨薇薇 , 等 . 侵袭性真菌病患者伏立康唑不良反应分析及临床处理经验 [J ] . 中国现代应用药学 , 2022 , 39 ( 3 ): 391 - 394 .
Chen X , He R , Yang WW , et al . Analysis of adverse reactions and clinical treatment experience of voriconazole in patients with invasive fungal disease [J ] . Chin J Mod Appl Pharm , 2022 , 39 ( 3 ): 391 - 394 .
李 祥 , 苏铎华 , 邢贞建 , 等 . CYP2C19基因多态性对预测侵袭性肺曲霉病患者伏立康唑相关不良反应的作用 [J ] . 实用医学杂志 , 2021 , 37 ( 9 ): 1168 - 1171 .
Li X , Su DH , Xing ZJ , et al . Voriconazole related adverse drug reactions among different CYP2C19 genes in patients with Aspergillusinfection [J ] . J Pract Med , 2021 , 37 ( 9 ): 1168 - 1171 .
De Pauw B , Walsh TJ , Donnelly JP , et al . Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group(EORTC/MSG)Consensus Group [J ] . Clin Infect Dis , 2008 , 46 ( 12 ): 1813 - 1821 .
Chen K , Zhang XL , Ke XY , 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 .
重症患者侵袭性真菌感染诊断与治疗指南(2007) [J ] . 中华内科杂志 , 2007 , 46 ( 11 ): 960 - 966 .
Guidelines for diagnosis and treatment of invasive fungal infection in severe patients(2007) [J ] . Chin J Intern Med , 2007 , 46 ( 11 ): 960 - 966 .
王 辰 , 高占成 . 内科学-呼吸与危重症医学分册 [M ] . 北京 : 人民卫生出版社 , 2016 : 35 - 42 .
Wang C , Gao ZC . Internal medicine-respiratory and critical care medicine [M ] . Beijing : People's Medical Publishing House , 2016 : 35 - 42 .
National Cancer Institute . Common Terminology Criteria for Adverse Events(CTCAE) version 5.0 [J/OL ] . [ 2017-11-27 ] . https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf .
Johnson LB , Kauffman CA . Voriconazole:a new triazole antifungal agent [J ] . Clin Infect Dis , 2003 , 36 ( 5 ): 630 - 637 .
肖桂荣 , 刘真真 , 唐光敏 . 隐球菌脑膜炎患者伏立康唑脑脊液浓度与血液浓度的临床分析 [J ] . 四川大学学报(医学版) , 2023 , 54 ( 1 ): 192 - 197 .
Xiao GR , Liu ZZ , Tang GM . Clinical analysis of voriconazole concentrations in cerebrospinal fluid and blood in patients with ryptococcal meningitis [J ] . J Sichuan Univ Med Sci , 2023 , 54 ( 1 ): 192 - 197 .
Laverdiere M , Bow EJ , Rotstein C , et al . Therapeutic drug monitoring for triazoles:a needs assessment review and recommendations from a Canadian perspective [J ] . J Can Des Maladies Infect De La Microbiol Med , 2014 , 25 ( 6 ): 327 - 343 .
Jin HY , Wang TS , Falcione BA , et al . Trough concentration of voriconazole and its relationship with efficacy and safety:a systematic review and Meta-analysis [J ] . J Antimicrob Chemother , 2016 , 71 ( 7 ): 1772 - 1785 .
程 林 , 梁再明 , 刘职瑞 , 等 . 伏立康唑致神经系统不良反应的临床特征及低血钾和低血钠发生情况 [J ] . 中国药房 , 2021 , 32 ( 20 ): 2520 - 2524 .
Cheng L , Liang ZM , Liu ZR , et al . Clinical characteristics of voriconazole-induced neurological ADR and the occurrence of hypokalemia and hyponatremia [J ] . China Pharm , 2021 , 32 ( 20 ): 2520 - 2524 .
罗 莉 , 文富强 . 慢性阻塞性肺疾病患者并发侵袭性肺曲霉病的影响因素研究 [J ] . 四川大学学报(医学版) , 2010 , 41 ( 4 ): 720 - 722 .
Luo L , Wen FQ . Study on influencing factors of invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease [J ] . J Sichuan Univ Med Sci Ed , 2010 , 41 ( 4 ): 720 - 722 .
王蓓蓓 , 许霞青 , 谭 然 , 等 . 73例肺曲霉病患者伏立康唑血药浓度监测及分析 [J ] . 中国新药与临床杂志 , 2022 , 41 ( 4 ): 228 - 233 .
Wang BB , Xu XQ , Tan R , et al . Voriconazole blood concentration monitoring and analysis in 73 patients with pulmonary aspergillosis [J ] . Chin J New Drugs Clin Remedies , 2022 , 41 ( 4 ): 228 - 233 .
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 .
陈 凡 , 胡述立 , 刘剑敏 , 等 . 伏立康唑相关肝损伤的真实世界研究 [J ] . 中国医院药学杂志 , 2021 , 41 ( 19 ): 2006 - 2010 .
Chen F , Hu SL , Liu JM , et al . Liver injury associated with voriconazole:a real-world study [J ] . Chin J Hosp Pharm , 2021 , 41 ( 19 ): 2006 - 2010 .
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 .
Cheng L , Weng BB , Xiang RF , et al . Relationship between voriconazole trough concentration and liver injury in elderly patients with lung invasive aspergillosis [J ] . J Third Mil Med Univ , 2020 , 42 ( 19 ): 1944 - 1949 .
王耀辉 , 张 英 , 朱建芸 , 等 . 血清降钙素原及中性粒细胞百分比对肝硬化失代偿期合并细菌感染的早期诊断价值 [J ] . 中山大学学报(医学版) , 2018 , 39 ( 3 ): 413 - 419 .
Wang YH , Zhang Y , Zhu JY , et al . Value of serum procalcitonin and percentage of neutrophils in early diagnosis of bacterial infection in decompensated liver cirrhosis [J ] . J Sun Yat Sen Univ Med Sci , 2018 , 39 ( 3 ): 413 - 419 .
Cheng L , Xiang RF , Liu F , et al . Therapeutic drug monitoring and safety of voriconazole in elderly patients [J ] . Int Immunopharmacol , 2020 , 78 : 106078 .
Ruiz J , Gordon M , Villarreal E , et al . Impact of voriconazole plasma concentrations on treatment response in critically ill patients [J ] . J Clin Pharm Ther , 2019 , 44 ( 4 ): 572 - 578 .
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