成人伏立康唑个体化用药监测分析  

Individualized medication monitoring of voriconazole in adults

作　　者：王希斌[1] 刘滔滔[1] 程道海[1] 黄春[1] 覃福礼 伍云 万瑞融[1] Wang Xibin;Liu Taotao;Cheng Daohai;Huang Chun;Qin Fuli;Wu Yun;Wang Ruirong(Department of Pharmacy,The First Affiliated Hospital of Guangxi Medical University;School of Pharmacy,Guangxi Medical University)

机构地区：[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

出　　处：《重庆医科大学学报》2023年第6期721-725,共5页Journal of Chongqing Medical University

基　　金：广西壮族自治区卫生健康委员会科研课题资助项目(编号:Z20200996)。

摘　　要：目的: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: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:(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0.5~5.0μg/mL,均数为2.7μg/mL;4/107(3.7%)血液标本的谷浓度<0.5μg/mL,均数为0.3μg/mL;41/107(38.4%)血液标本的谷浓度>5.0μg/mL,中位数为8.7μg/mL。(2)谷浓度<0.5μg/mL组、谷浓度≥0.5μg/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<0.5μg/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。(3)10例(15.8%)发生不良反应,谷浓度>5.0μg/mL的患者与谷浓度≤5.0μg/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≤5.0μg/mL的患者组与谷浓度>5.0μg/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>5.0μg/mL时,抗感染治疗后,降钙素原(procalcitonin,PCT)明显降低(P<0.05)。结论: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: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: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:After treatment with voriconazole at the conventional dose,the trough concentration of voriconazole was 0.5-5.0μg/mL in 57.9%(62/107)of the samples,with a averge concentration of 2.7μg/mL;the trough concentration of voriconazole was<0.5μg/mL in 3.7%(4/107)of the samples,with a averge concentration of 0.3μg/mL;the trough concentration of voriconazole was>5.0μg/mL in 38.4%(41/107)of the samples,with a median concentration of 8.7μg/mL.The patients with a trough concentration of<0.5μg/mL had a response rate of 50.0%,while those with a trough concentration of≥0.5μg/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<0.5μg/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>5.0μg/mL and 14.6%in those with a trough concentration of≤5.0μg/mL,with the main adverse reaction of abn

关 键 词：伏立康唑 药物监测 不良反应 个体化给药 

分 类 号：R969.1[医药卫生—药理学]