五水头孢唑林钠群体药代动力学研究

Population pharmacokinetics model of cefazolin sodium pentahydrate in Chinese adult patients

目的研究注射用五水头孢唑林钠在感染患者中的群体药代动力学(PPK)。方法 PPK研究在感染患者或者需要手术前预防感染的患者中进行,采集每个患者在静脉滴注五水头孢唑林钠2 g后0~48 h内的4~5个血样,用液相色谱法测定血药浓度,以非线性混合效应模型(NONMEN)程序建立并验证五水头孢唑林钠的群体药代动力学模型。结果根据文献资料及所测定血药浓度数据建立二室PPK模型,五水头孢唑啉钠清除率(CL)、中央室分布容积(V1)及外周室分布容积(V2)分别为3.24 L·h^(-1)、10.78 L、8.62 L,患者体重对CL具有显著影响,性别、年龄和给药剂量均不影响其药代动力学参数。结论用NONMEM软件拟合建立的五水头孢唑林钠PPK模型是稳定、有效的,可用于感染患者个体化药代动力学参数估算。

Objective To establish a population pharmacokinetic model of cefazolin sodium pentahydrate in Chinese adult patients. Methods A total of 180 plasma samples and clinical data were collected from 40 patients diagnosed or suspected bacterial infection. The concentration of cefazolin was determined by HPLC,and a population pharmacokinetics mode（ PPK） was established and validated using nonlinear mixed effect model（ NONMEN） software after obtaining PPK parameters. Results Based on literature and the determined concentrations,a two- compartment PPK model was established,the population value of clearance（ CL）,distribution volumes of central（ V1） and peripheral compartment（ V2） were 3. 24 L·h- 1,10. 78 L,8. 62 L,respectively. The weight of patient had a significant influence on the CL,while the other factors such as sex,age and daily dose of administration had no marked effect on the pharmacokinetic parameters of cefazolin sodium pentahydrate.Conclusion The population pharmacokinetic model of cefazolin sodium pentahydrate using NONMEN was stable and effective,which could be used to estimate the individual pharmacokinetic parameter for patients and to design a prior dosage regimen.