泊沙康唑口服混悬液在HSCT患者中的剂量校正浓度及其影响因素分析  

Dose-adjusted concentrations of Posaconazole oral suspension in hematopoietic stem cell transplantation patients and analysis of the influential factors

作　　者：董琳[1] 束一朔 董中华 衣巧艳 李洪娟[3] 顾艳[3] 韩燕 丁国玉[3] 赵羽琦 张潇月 李雪 林子云 穆锴 杨依磊 时海燕[2] 王红美[3] DONG Lin;SHU Yishuo;DONG Zhonghua;YI Qiaoyan;LI Hongjuan;GU Yan;HAN Yan;DING Guoyu;ZHAO Yuqi;ZHANG Xiaoyue;LI Xue;LIN Ziyun;MU Kai;YANG Yilei;SHI Haiyan;WANG Hongmei(Dept.of Hematology,the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital),Jinan 250014,China;Dept.of Clinical Pharmacy,the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital)/Shandong Engineering and Technology Research Center for Pediatric Drug Clinical Evaluation and Development/Shandong Medicine and Health Key Laboratory of Clinical Pharmacy,Jinan 250014,China;Dept.of Pediatrics,the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital)/Shandong Engineering and Technology Research Center for Pediatric Drug Clinical Evaluation and Development,Jinan 250014,China)

机构地区：[1]山东第一医科大学第一附属医院(山东省千佛山医院)血液病学科,济南250014 [2]山东第一医科大学第一附属医院(山东省千佛山医院)临床药学科/山东省儿童药物临床评价与研发工程技术研究中心/山东省医药卫生临床药学重点实验室,济南250014 [3]山东第一医科大学第一附属医院(山东省千佛山医院)小儿内科/山东省儿童药物临床评价与研发工程技术研究中心,济南250014

出　　处：《中国药房》2023年第24期3025-3029,共5页China Pharmacy

基　　金：国家重点研发计划项目(No.2020YFC2008303,No.2020YFC2008306)。

摘　　要：目的分析泊沙康唑口服混悬液在造血干细胞移植(HSCT)患者中的剂量校正浓度,并分析其影响因素。方法收集2021年1月至2023年4月山东第一医科大学第一附属医院(山东省千佛山医院)收治的服用泊沙康唑口服混悬液预防侵袭性真菌病(IFD)并行泊沙康唑血药浓度监测的住院HSCT患者的临床资料。评估泊沙康唑预防IFD的浓度达标率和临床失败率,并对该药剂量校正浓度(C0/D)的影响因素进行单因素和多元线性回归分析。结果共纳入44例患者,患者的泊沙康唑平均谷浓度(C0)为(0.99±0.94)μg/mL,有20例患者的C0不低于0.7μg/mL,泊沙康唑预防IFD的浓度达标率为45.45%;13例为临床失败,临床失败率为29.55%。在C0未达标的24例患者中,有7例患者及时调整了泊沙康唑剂量,但仍有1例为临床失败;13例未进行剂量调整的患者中,有7例为临床失败;其余4例患者更换了抗真菌药物。单因素分析结果显示,患者性别、体重指数(BMI)、肾功能和联用苯妥英钠、奥美拉唑、甲氧氯普胺对泊沙康唑C0/D有显著影响(P<0.05);多元线性回归分析结果显示,性别、BMI和联用苯妥英钠是影响泊沙康唑C0/D的独立因素(P<0.05)。结论泊沙康唑口服混悬液血药浓度个体差异较大;性别、BMI和联用苯妥英钠是影响泊沙康唑C0/D的独立因素。OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation(HSCT)and their influential factors.METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University(Shandong Provincial Qianfoshan Hospital)from January 2021 to April 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease(IFD)and received blood concentration of posaconazole.The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated,and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations(C0/D)of posaconazole.RESULTS A total of 44 patients were enrolled;the mean C0 of posaconazole in patients was(0.99±0.94)μg/mL,and 20 patients had a C0≥0.7μg/mL,with a concentration attainment rate of 45.45%for the prevention of IFD;13 cases were clinical failures,with a clinical failure rate of 29.55%.Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis,one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients;seven of the thirteen patients who did not undergo dose adjustment were clinical failures;and the remaining four patients were switched to other antifungal agents.The results of univariate analysis showed that gender,body mass index(BMI),renal function,combined use of sodium phenytoin,omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole(P<0.05);the results of multivariate linear regression analysis showed that gender,BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole(P<0.05).CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension;gender,BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posacon

关 键 词：泊沙康唑 剂量校正浓度 影响因素 造血干细胞移植 治疗药物监测 

分 类 号：R978.5[医药卫生—药品]