中国临床药学杂志2025，Vol.34Issue(1)：33-39,7.DOI:10.19577/j.1007-4406.2025.01.006
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
摘要
Abstract
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,Cavg,ss,Cavg,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 Aspergillus 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 terreus,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 suspension group(P＜0.01).The average age,trough concentrations,Cavg,ss and AUC in the posaconazole suspension group from pediatric patients were lower than those in the enteric-coated tablet group(P＜0.01).The CL/F of pediatric patients treated with posaconazole suspension was higher than that of enteric-coated tablets(P＜0.01).The AUC/MIC values of posaconazole enteric-coated tablets against Candida,Aspergillus fumigatus and Aspergillus terreus,and other Aspergillus species in pediatric patients were 1 008.34±342.65,242.00±82.24 and 121.00±41.12 respectively.For the suspension of posaconazole in pediatric patients,the AUC/MIC values against Candida,Aspergillus fumigatus and Aspergillus terreus,and other Aspergillus species were 486.14±137.25,116.67±32.94 and 58.34±16.47 respectively.The compliance rates to achieve the target trough concentration of Cavg,ss were 99.25％for adult patients in enteric-coated tablet group and 16.67％for adult patients in the suspension group.After adjusting the dosing regimen for adult patients in the posaconazole suspension group who initially failed to meet the target trough concentration of Cavg,ss,the compliance rate of the target trough concentration of Cavg,ss significantly improved from 16.67％to 66.67％.CONCLUSION The PK/PD of posaconazole enteric-coated tablets and suspension in ill adults and children was studied based on the Bayesian feedback method.This method was applied to dose adjustment and optimization of individual patients,which could enhance the efficacy and contribute to guide the clinical rational medication.关键词
泊沙康唑/药品剂型/药动学/药效学/个体化给药Key words
posaconazole/dosage form/pharmacokinetic/pharmacodynamic/individualized administration分类
药学引用本文复制引用
何娟,程研,谭春丽,张梦师,高永跃,王诗淞,旦增达瓦,陈尔真,王义辉..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[J].中国临床药学杂志,2025,34(1):33-39,7.基金项目
中华国际医学交流基金会(编号RC20200120) （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]) （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]) （联合）
