中性粒细胞缺乏患者万古霉素群体药代动力学模型的建立  

Establishment of population pharmacokinetics model of vancomycin in patients with Neutropenia

作　　者：林良沫 符祥俊[2] 钟莉莉[2] 王和芳[2] 吴琼诗[2] 肖坚[1,3] LIN Liangmo;FU Xiangjun;ZHONG Lili;WANG Hefang;WU Qiongshi;XIAO Jian(Central South University,Changsha 410008,Hunan,China;Hainan General Hospital(Hainan Affiliated Hospital of Hainan Medical University),Haikou 570311,Hainan,China;Xiangya Hospital of Central South University,Changsha 410008,Hunan,China)

机构地区：[1]中南大学,湖南长沙410008 [2]海南省人民医院(海南医学院附属海南医院),海南海口570311 [3]中南大学湘雅医院,湖南长沙410008

出　　处：《中国临床药理学与治疗学》2021年第9期1014-1022,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：海南省卫生计生行业科研项目(20A200280)。

摘　　要：目的:建立血液病伴中性粒细胞缺乏患者的万古霉素群体药代动力学(PPK)模型。方法:收集我院血液内科静脉使用万古霉素的中性粒细胞缺乏成人患者(n=77)的临床资料和用药信息,监测万古霉素血药谷浓度和峰浓度,使用非线性混合效应模型(NONMEM)的建模方法建立该人群的万古霉素PPK模型并进行评估和验证。结果:所建模型为二室模型,最终模型公式为:清除率CL=6.84×(BW/70)^(0.75)×(CLCR/116)^(0.895)×exp(η_(1)),中央室分布容积V_(1)=20.5×(BW/70)×exp(η_(2)),室间转运速率Q=15.2×(BW/70)^(0.75)×exp(η_(3)),外周室分布容积V_(2)=50×(BW/70)×exp(η_(4)),(BW为体质量,CLCR为肌酐清除率)。采用拟合优度图和模型预测诊断图以及非参数Bootstrap法进行模型的内部验证,采用26个相同入组条件的患者数据进行外部验证,表明模型具有良好的稳定性和准确性。结论:建立血液病伴中性粒细胞缺乏患者的万古霉素PPK模型,有助于实现该人群万古霉素的个体化应用。AIM:To establish a population pharmacokinetics(PPK)model of vancomycin in patients with hematological diseases who developed neutropenia.METHODS:Patients from department of hematology with neutropenia in our hospital were taken into oue study.The patients(n=77)were performed trough and peak serum concentration of vancomycin,and their clinical data and medication information were collected.The Nonlinear mixed effect modeling approach(NONMEM)was used to establish the PPK model of those patients and model assessment and validation was carried out.Goodneess of fit plots and visual predictive check plus Bootstrap approach were used to assess validate our model.RESULTS:The model was a two compartment model,the final formulas were:clearance rate CL=6.84×(BW/70)^(0.75)×(CLCR/116)^(0.895)×exp(η_(1)),distribution volume of central ventricle V_(1)=20.5×(BW/70)×exp(η_(2)),transport rate Q=15.2×(BW/70)^(0.75)×exp(η_(3)),distribution volume of peripheral ventricle V_(2)=50×(BW/70)×exp(η_(4)),(BW was body weight,CLCR was creatinine clearance rate).Additionally 15 patients with neutropenia were included to conduct external validation,and it showed good stability and accuracy.CONCLUSION:The establishment of PPK model of vancomycin in patients with hematologic diseases who developed neutropenia is helpful to realize the individualized application of vancomycin in this population.

关 键 词：中性粒细胞缺乏 万古霉素 群体药代动力学模型 

分 类 号：R969[医药卫生—药理学]