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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 study the population pharmacokinetics (PPK) of cefazolin sodium pentahydrate in infected patients. Methods The PPK study was performed in patients with or before infection requiring prophylaxis. Four to five blood samples from 0 to 48 hours after intravenous instillation of 2 g of cefazolin sodium in each patient were collected and analyzed by liquid chromatography Method was used to determine the plasma concentration. A population pharmacokinetic model of cefazolin sodium pentahydrate was established and validated by the non-linear mixed-effects model (NONMEN) program. Results According to the literature data and the measured plasma concentration data, a two-compartment PPK model was established. The clearance rate of cefazolin sodium pentahydrate (CL), the distribution volume of central compartment (V1) and the distribution volume of peripheral compartment (V2) were 3.24 L · h ~ (-1), 10.78 L, 8.62 L, body weight of patients had a significant effect on CL, sex, age and dose did not affect its pharmacokinetic parameters. Conclusion The PPK model of cefazolin sodium pentahydrate fitted by NONMEM software is stable and effective and can be used to estimate the individual pharmacokinetic parameters of infected patients.