药代-药效学建模分析金黄色葡萄球菌在不同喹诺酮类抗菌药物浓度下的生长曲线  

A pharmacokinetic-pharmacodynamic model characterizing the growth curves of Staphylococcus aureus under different quinolone concentrations

作　　者：魏敏吉[1] 李耘[1] 吕媛[1] Wei Min-ji;Li Yun;LüYuan(Institute of Clinical Pharmacology,First Hospital,Peking University,Beijing 100191)

机构地区：[1]北京大学第一医院临床药理研究所

出　　处：《中国抗生素杂志》2020年第1期69-72,共4页Chinese Journal of Antibiotics

摘　　要：目的利用数学模型拟合金黄色葡萄球菌(金葡菌)在不同喹诺酮类药物的最低抑菌浓度(minimum inhibitory concentration,MIC)倍数浓度下的生长曲线,求得关键的药效学参数,为抗菌药物的PK/PD研究提供支持。方法获得3种喹诺酮类药物-西他沙星、莫西沙星和左氧氟沙星,在不同MIC值下的细菌生长曲线,利用非线性混合效应估计(nonlinear mixed-effect estimation,NLME)数学模型进行了拟合。结果所建立的模型可以对不同药物MIC值下的生长曲线进行拟合,并可获得主要的药效学参数,包括PK/PD指数、PK/PD靶值。结论所选择的数学模型可以用于拟合金葡菌在不同药物浓度下的生长曲线,得到的PK/PD(AUC/MIC)靶值,且与采用其他方法所获得的结果具有可比性。Objective To fit the growth curves of Staphylococcus aureus under different folds of minimum inhibitory concentration(MIC)values of quinolones and obtain pivotal pharmacodynamic parameters to support the pharmacokinetic-pharmacodynamic(PK/PD)studies on quinolones.Methods Growth curves of Staphylococcus aureus under concentrations of three different quinolones-sitafloxacin,levofloxacin,and moxifloxacin,were obtained under standard procedures.A pharmacokinetic-pharmacodynamic model using nonlinear mixed-effect estimation(NLME)was constructed to fit the curves.Results The pharmacokinetic-pharmacodynamic model was successfully used in the fitting of growth curves of Staphylococcus aureus under different quinolone concentrations.Pivotal pharmacokinetic-pharmacodynamic parameters such as PK/PD index and PK/PD target were obtained.Conclusion The constructed mathematical model could be used for the curve fitting,the obtained PK/PD target were comparable to the results reported in literatures using other methods.

关 键 词：喹诺酮类 细菌生长曲线 药代/药效模型 数学模型 

分 类 号：R969[医药卫生—药理学]