重症患者泊沙康唑的药动学/药效学研究及临床应用效果分析  

Pharmacokinetic/pharmacodynamic study and clinical efficacy analysis of posaconazole in critically ill patients

作　　者：何娟[1] 程研 谭春丽 张梦师 高永跃 王诗淞 旦增达瓦 陈尔真[8] 王义辉 HE Juan;CHENG Yan;TAN Chunli;ZHANG Mengshi;GAO Yongyue;WANG Shisong;DANZENG Dawa;CHEN Erzhen;WANG Yihui(Department of Pharmacy,Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200025,China;Department of Pharmacy,Zaozhuang Central Hospital Affiliated to Shandong Guoxin Yiyang Group,Zaozhuang 277000,China;Department of Pharmacy,Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China;Department of Pharmacy,Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,China;Department of Pharmacy,Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550002,China;Department of Pharmacy,Hainan Qionghai People's Hospital,Qionghai 571400,China;Department of Emergency,Shigatse People's Hospital,Shigatse 857000,China;Department of Emergency,Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200025,China)

机构地区：[1]上海交通大学医学院附属瑞金医院药剂科,上海200025 [2]山东国欣颐养集团枣庄中心医院药剂科,枣庄277000 [3]广西壮族自治区人民医院药学部,南宁530021 [4]广西右江民族医学院附属医院药学部,百色533000 [5]贵州中医药大学第二附属医院,550002 [6]海南省琼海市人民医院药剂科,琼海571400 [7]西藏自治区日喀则市人民医院急诊科,日喀则857000 [8]上海交通大学医学院附属瑞金医院急诊科,上海200025

出　　处：《中国临床药学杂志》2025年第1期33-39,共7页Chinese Journal of Clinical Pharmacy

基　　金：中华国际医学交流基金会(编号RC20200120);西藏自治区自然科学基金组团式援藏医学项目(编号XZ2023ZR-ZY35[Z]);日喀则市自然科学基金(联合)项目(编号RKZ2023ZR-013[Z],RKZ2023ZR-017[Z])。

摘　　要：目的 探讨重症成人和儿童患者泊沙康唑的药动学/药效学(PK/PD)特征,并分析其临床应用效果。方法 收集2020年1月至2022年12月住院接受泊沙康唑治疗并进行泊沙康唑血药谷浓度测定的成人和儿童病例共298例,分为泊沙康唑肠溶片组210例和泊沙康唑混悬液组88例。采用贝叶斯反馈法估算PK参数[表观分布容积(Vd)、清除率(CL/F)等],绘制药-时曲线,计算药-时曲线下面积(AUC)。记录微生物培养和药敏结果,以及泊沙康唑对念珠菌、烟/土曲霉及其他曲霉的最低抑菌浓度(MIC),计算AUC/MIC。根据PK/PD结果,对泊沙康唑混悬液组初始谷浓度未达标成人病例的给药方案进行调整,计算调整后的谷浓度达标率。结果 泊沙康唑混悬液组成人病例的年龄、谷浓度、Cavg,ss、Cavg,ss达标率和AUC均低于泊沙康唑肠溶片组(P <0.01),CL/F高于泊沙康唑肠溶片组(P <0.01)。泊沙康唑肠溶片组成人病例念珠菌、烟/土曲霉和其他曲霉的AUC/MIC分别为653.43±228.54、156.82±54.85和78.41±27.43;混悬液组成人病例念珠菌、烟/土曲霉和其他曲霉的AUC/MIC分别为181.61±45.58、43.59±10.94和21.79±5.47,泊沙康唑肠溶片组成人病例各真菌的AUC/MIC均高于混悬液组(P<0.01)。泊沙康唑混悬液组儿童病例的年龄、谷浓度、Vd/F、Cavg,ss和AUC均低于泊沙康唑肠溶片组(P <0.01),CL/F高于泊沙康唑肠溶片组(P<0.01)。泊沙康唑肠溶片组儿童病例念珠菌、烟/土曲霉和其他曲霉的AUC/MIC分别为1 008.34±342.65、242.00±82.24和121.00±41.12;混悬液组儿童病例念珠菌、烟/土曲霉和其他曲霉的AUC/MIC分别为486.14±137.25、116.67±32.94和58.34±16.47,泊沙康唑肠溶片组儿童病例各真菌的AUC/MIC均高于混悬液组(P <0.01)。泊沙康唑肠溶片组成人病例的Cavg,ss达标率为99.25%,泊沙康唑混悬液组成人病例的Cavg,ss达标率为16.67%。对泊沙康唑混悬液组Cavg,ss未达标的成人病例进行给药方案调AIM To investigate the pharmacokinetic(PK)/pharmacodynamic(PD) of posaconazole in critically ill adults and children,and to analyze its clinical application effect.METHODS A total of 298 hospitalized adult and pediatric patients receiving posaconazole treatment in the hospital were selected and assigned to enteric-coated tablet group with 210 patients and suspension group with 88 patients.The Bayesian approach was utilized to determine pharmacokinetic parameters,including the apparent volume of distribution(Vd) and the clearance rate(CL/F).Subsequently,the drug-time profile was constructed,and the area under the curve(AUC) was computed.Microbial culture and susceptibility results were collected,and the minimum inhibitory concentration(MIC) data for posaconazole against Candida,Aspergillus fumigatus and Aspergillus terreus,and other Aspergillus species were recorded,with the AUC/MIC ratio being calculated.Based on the PK/PD results,the regimen adjustments were made for adult patients in the posaconazole suspension group where the initial trough concentrations failed to meet the standard,and the compliance rate of target trough concentrations was calculated.RESULTS The average age,trough concentrations,C_(avg,ss),C_(avg,ss) compliance rate and AUC in the posaconazole suspension group from adult patients were lower than those in the enteric-coated tablet group(P<0.01),and the CL/F was higher than that in the enteric-coated tablet group(P<0.01).The AUC/MIC values of posaconazole enteric-coated tablets against Candida,Aspergillus fumigatus and Aspergillus terreus,and other species in adult patients were 653.43±228.54,156.82±54.85,and 78.41±27.43 respectively.For the suspension of posaconazole in adult patients,the AUC/MIC values against Candida,Aspergillus fumigatus and Aspergillus ter reus,and other Aspergillus species were 181.61±45.58,43.59±10.94,and 21.79±5.47 respectively.The AUC/MIC values of posaconazole enteric-coated tablets against various fungi in adult patients were all higher than those of the suspe

关 键 词：泊沙康唑 药品剂型 药动学/药效学 个体化给药 

分 类 号：R978.5[医药卫生—药品]