西他沙星在呼吸道感染患者中的群体药动学分析与剂量优化  

Population Pharmacokinetic Analysis and Dose Optimization of Sitafloxacin in Patients with Respiratory Infections

作　　者：魏丽春 WEI Li-chun(Department of Pharmacy,Pingtan Comprehensive Experimental Area Hospital,Pingtan 350400,China)

机构地区：[1]平潭综合实验区医院,福建平潭350400

出　　处：《海峡药学》2024年第12期123-128,共6页Strait Pharmaceutical Journal

摘　　要：目的建立呼吸道感染患者中西他沙星的群体药动学模型(population pharmacokinetics,PopPK)。方法在Phoenix NLME程序中采用非线性混合效应模型建立西他沙星的PopPK模型。通过拟合优度图、bootstrap和可视化预测检验图评估模型的拟合程度、有效性、稳定性和预测性能,并使用蒙特卡洛模拟预测不同最低抑菌浓度下多组剂量的达标概率。结果收集了145例呼吸道感染患者的366个血浆样本。单室模型充分描述了西他沙星在该患者群体中的药动学特性。表观分布容积、清除率和吸收速率常数的典型值分别为1.01 L·kg^(-1)、18.08 L·h^(-1)和3.98 h^(-1)。蒙特卡洛模拟结果显示,低剂量(≤50 mg)仅适用于病原体极度敏感时(如MIC=0.25 mg·L^(-1)),若MIC达到1 mg·L^(-1),建议将剂量提高至100 mg q12h或更多。结论本研究提供了呼吸道感染患者中西他沙星的PopPK模型,为个体化用药提供了参考。OBJECTIVE To establish a population pharmacokinetics(PopPK)model of sitafloxacin in patients with respiratory infections.METHODS A PopPK model for sitafloxacin was developed using a nonlinear mixed-effects model in Phoenix NLME.Model fitting,validity,stability,and predictive performance were evaluated through goodness-of-fit plots,bootstrap,and visual predictive checks.Monte Carlo simulations were used to predict the probability of target attainment for multiple dosing regimens at different minimum inhibitory concentration values.RESULTS A total of 145 patients with respiratory infections provided 366 plasma samples.A one-compartment model adequately described the pharmacokinetics of sitafloxacin in this patient population.The typical values for apparent volume of distribution,clearance,and absorption rate constant were 1.01 L·kg^(-1),18.08 L·h^(-1),and 3.98 h^(-1),respectively.Monte Carlo simulation results indicated that low doses(≤50 mg)are suitable only when the pathogen is highly sensitive(MIC≤0.25 mg·L^(-1)).For an MIC of 1 mg·L^(-1),a dose increase to 100 mg q12h or more is recommended.CONCLUSION This study provides a PopPK model of sitafloxacin for patients with respiratory infections,offering a reference for individualized dosing.

关 键 词：西他沙星 群体药动学 呼吸道感染 

分 类 号：R965[医药卫生—药理学]