基于群体药动学的万古霉素个体化给药模式的建立和临床应用

详细信息    查看官网全文

• 英文论文题名：Clinical individualization for infected patients based on Population pharmacokinetics model of vancomycin
• 论文作者：何娟 ; 杨婉花
• 英文论文作者：He Juan ; YANG Wan-Hua ; Department of Pharmacy of Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine
• 年：2016
• 作者机构：上海交通大学医学院附属瑞金医院药剂科;
• 论文关键词：万古霉素 ; JPKD ; 群体药动学 ; 贝叶斯反馈法 ; 个体化给药
• 英文论文关键词：Vancomycin ; JPKD ; Population pharmacokinetics(PPK) ; Bayesian algorithm ; Clinical individualization
• 会议召开时间：2016-09-27
• 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
• 语种：中文
• 分类号：R969.1
• 学会代码：YYWS
• 会议名称：中国药学会第十三届青年药学科研成果交流会
• 会议地点：中国江西南昌
• 主办单位：中国药学会
• 学会名称：中国药学会
• 页数：6
• 文件大小：401k
• 原文格式：O
• 会议级别：全国

摘要

目的:评估万古霉素群体药动学软件(JPKD-vancomycin)在中国人群的预测能力,并验证其临床应用效果。方法:根据万古霉素群体药动学(PPK)研究模型,在JPKD的自定义板块重新定义新的万古霉素药动学模型。利用Bayesian方法估算万古霉素药动学参数。收集我院接受万古霉素治疗的住院患者,排除严重肾功能不全者(肌酐清除率小于50ml/min)以及合并用药者(甘露醇、多巴胺、多巴酚丁胺、呋塞米),筛选出有作万古霉素剂量调整且有稳态谷浓度测定数据者68例。将患者第一次的万古霉素给药剂量及相关的个体化信息输入JPKD-vancomycin,使用Bayesian法估算出患者个人的药动学参数,再输入第二次的万古霉素给药剂量,输注时间和给药间隔,由软件依据上述参数预测出更改剂量后的谷浓度数据,计算预测浓度(PRED)与实测浓度(DV)的权重偏差(WRES),考察该软件的预测能力,并通过临床病例验证。结果:所有患者使用万古霉素后的实际稳态谷浓度平均值为11.71±5.15μg·mL~(-1),以JPKD-vanconycin运算后预测的谷浓度平均值为11.55±5.19μg·mL~(-1),WRES为11.6%±7.9%。模型对中国人群的预测能力良好;经临床初步验证,效果较为满意。结论:JPKD-vancomycin对中国人群万古霉素稳态谷浓度有良好的预测能力。本研究建立的JPKD-vancomycin个体化给药模式,有助于临床合理用药。
Objective To establish the clinical application mode of the Population pharmacokinetics(PPK) model of vancomycin(VCM).Method A new PPK model of JPKD-vancomycin was established.Steady-state trough concentration of VCM from 68 infected patients was collected to develop pharmacokinetic parameters,and the individualized protocol and predicted steady-state trough concentration was calculated using the patient information such as age,body weight,et al,according to Bayesian evaluation.Patients with severe kidney failure(creatinine clearance rate < 50ml/min) and concomitant medicine like Mannitol,dopamine,dobutamine,furosemide were excluded.The Weight deviation(WRES) was calculated according to the formula:WRES= | PRED-DV | /DV×100%,to evaluate predictive ability of the model.Bayesian forecasting program for individualized dosing was written to explore the way of applying VCM PKK model in clinic.Result The average trough concentration from the 68 infected patients was 11.71 ± 5.15μg·mL~(-1) while the average predicted trough concentration from JPKD-vancomycin was 11.55± 5.19μg·mL~(-1),WRES was 11.6%± 7.9%.The final model had positive prediction for the samples from Chinese population.This study primarily established clinical appUcation pattern of VCM PKK model,and this model could be used for VCM individualized medication.Conclusion The mode of clinical appUcation based on Bayesian forecasting process of JPKD-vancomycin model had positive prediction for the samples from Chinese population,and could help assist cUnical individualized appUcation of VCM.

引文

[1]Liu C,Bayer A,Cosgrove SE,Daum RS,Fridkin SK,Gorwitz RJ,et al..Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children[Journal Article;Practice Guideline;Research Support,Non-U.S.Gov't].Clin Infect Dis 2011;52(3):el8-55.eng.
    [2]Rybak M,Lomaestro B,Rotschafer JC,Moellering RJ,Craig W,Billeter M,et al..Therapeutic monitoring of vancomycin in adult patients:a consensus review of the American Society of Health-System Pharmacists,the Infectious Diseases Society of America,and the Society of Infectious Diseases Pharmacists[Journal Article;Review].Am J Health Syst Pharm 2009;66(1):82-98.eng.
    [3]万古霉素临床应用中国专家共识(2011版).中国新药与临床杂志2011;(8):561-73.
    [4]Rybak M,Lomaestro B,Rotschafer JC,Moellering RJ,Craig W,Billeter M,et al..Therapeutic monitoring of vancomycin in adult patients:a consensus review of the American Society of Health-System Pharmacists,the Infectious Diseases Society of America,and the Society of Infectious Diseases Pharmacists[Journal Article;Review].Am J Health Syst Pharm 2009;66(1):82-98.eng.
    [5]Beibei L,Yun C,Mengli C,Nan B,Xuhong Y,Rui W.Linezolid versus vancomycin for the treatment of gram-positive bacterial infections:meta-analysis of randomised controlled trials[Comparative Study;Journal Article;Meta-Analysis;Review].Int J Antimicrob Agents 2010;35(1):3-12.eng.
    [6]Bounthavong M,Hsu DI.Efficacy and safety of linezolid in methicillin-resistant Staphylococcus aureus(MRSA)complicated skin and soft tissue infection(cSSTI):a meta-analysis[Journal Article;Meta-Analysis;Research Support,Non-U.S.Gov't].Curr Med Res Opin 2010;26(2):407-21.eng.
    [7]Shorr AF,Kunkel MJ,Kollef M.Linezolid versus vancomycin for Staphylococcus aureus bacteraemia:pooled analysis of randomized studies[Comparative Study;Journal Article;Meta-Analysis;Research Support,Non-U.S.Gov't].J Antimicrob Chemother 2005;56(5):923-29.eng.
    [8]Cai Y,Wang R,Liang B,Bai N,Liu Y.Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease[Journal Article;Meta-Analysis;Review].Antimicrob Agents Chemother2011;55(3):1162-72.eng.
    [9]Bliziotis IA,Plessa E,Peppas G,Falagas ME.Daptomycin versus other antimicrobial agents for the treatment of skin and soft tissue infections:a meta-analysis[Journal Article;Meta-Analysis;Review].Ann Pharmacother 2010;44(1):97-106.eng.
    [10]McClaine RJ,Husted TL,Hebbeler-Clark RS,Solomkin JS.Meta-analysis of trials evaluating parenteral antimicrobial therapy for skin and soft tissue infections[Journal Article;Meta-Analysis].Clin Infect Dis 2010;50(8):1120-26.eng.
    [11]Pea F,Bertolissi M,Di Silvestre A,et al.TDM coupled with Bayesian forecasting should be considered an invaluable tool for optimizing vancomycin daily exposure in unstable critically ill patients[J].International journal of antimicrobial agents,2002,20(5):326-332.
    [12]Buelga,D.S.,M.del Mar Fernandez de Gatta,et al.(2005).Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies.Antimicrob Agents Chemother 49(12):4934-41.