危重症患者替加环素的群体药动学

目的: 建立替加环素在危重症患者中的群体药动学模型,探究该类人群中影响替加环素药动学的因素。方法: 收集静脉使用替加环素的危重症患者的血样,使用高效液相色谱-质谱联用技术测定替加环素的血药浓度。利用NONMEM软件估算替加环素的药动学参数,通过向前纳入法和逆向剔除法建立替加环素群体药动学模型,并对该模型进行验证和评价。结果: 收集54名患者的143个血药浓度建立替加环素的群体药动学模型,静脉给药的一室模型较好地描述替加环素的药动学特征,替加环素的清除率(CL)、表观分布容积(V_d)的群体典型值分别为11.3 L·h^-1和105 L,患者的APACHE Ⅱ评分和年龄对模型有显著影响。结论: 建立的替加环素群体药动学模型预测性能稳定良好,APACHE Ⅱ评分影响替加环素CL,年龄影响替加环素V_d,可为临床替加环素在危重症患者中的个体化给药提供参考。

Population pharmacokinetics of tigecycline in critically ill patients

OBJECTIVE To establish a population pharmacokinetic model of tigecycline in critically ill patients and to explore the covariantes on the pharmacokinetics of tigecycline in this population.METHODS The blood samples of critically ill patients treated with tigecycline were collected and the plasma concentration of tigecycline was determined by liquid chromatography-mass spectrometry(LC-MS).The pharmacokinetic parameters of tigecycline were estimated by NONMEM software.The population pharmacokinetic model of tigecycline was established by forward inclusion method and reverse elimination method, then the final model was verified and evaluated.RESULTS The population pharmacokinetic model of tigecycline was established by using 143 blood samples collected from 54 patients.A one-compartment model of intravenous administration could well describe the pharmacokinetic characteristics of tigecycline.The population typical values of clearance(CL) and distribution volume(V_d) of tigecycline were 11.3 L·h^-1 and 105 L.APACHE Ⅱ scores and age have significant effects on the model.CONCLUSION The prediction performance of the established population pharmacokinetic model of tigecycline is stable and good.APACHE Ⅱ score affects tigecycline CL and age affects tigecycline V_d, which can provide a reference for clinical individual administration of tigecycline in critically ill patients.