茶碱在老年慢性阻塞性肺疾病患者中的群体药动学

发布时间：2018-08-04 13:08

【摘要】：目的:建立茶碱在老年慢性阻塞性肺疾病患者中的群体药动学(PPK)模型,并获取药动学参数,为临床制定个体化给药方案提供参考。方法:收集2014年4—12月某院诊断为慢性阻塞性肺疾病应用茶碱治疗的68例老年患者的血药浓度监测数据及临床资料,运用非线性混合效应模型法(NONMEN)定量分析性别、年龄、体质量及肝肾功能等因素对药动学参数的影响,最终建立PPK模型。采用拟合优度、自举法和可视化检验对最终模型的性能进行内部验证。结果:茶碱的药动学符合一室模型,最终模型公式为:CL=θ_(CL)×(WT/63)~(θWT)×exp(ηCL),V=θ_V×exp(ηV),其中的协变量为体质量,模型CL和V的群体典型值分别为0.849 L·h~(-1),13.7 L。拟合优度、自举法和可视化检验的评价结果表明最终模型稳定,预测结果可靠。结论:建立的PPK模型能较好地描述茶碱在老年慢性阻塞性肺疾病患者中的药动学特点,患者体质量对参数CL有显著性影响。
[Abstract]:Objective: to establish a group pharmacokinetic (PPK) model of theophylline in elderly patients with chronic obstructive pulmonary disease (COPD) and to obtain pharmacokinetic parameters so as to provide a reference for the clinical formulation of individualized regimen of administration of theophylline. Methods: the blood drug concentration monitoring data and clinical data of 68 elderly patients with chronic obstructive pulmonary disease diagnosed as chronic obstructive pulmonary disease from April to December 2014 were collected and analyzed quantitatively by (NONMEN) with nonlinear mixed effect model. The effect of body mass, liver and kidney function on pharmacokinetic parameters was studied. Finally, PPK model was established. The performance of the final model is verified internally by means of goodness of fit, bootstrap and visual test. Results: the pharmacokinetics of theophylline was in accordance with the one-compartment model. The final model formula was: 1: CL= 胃 _ (CL) 脳 (WT/63) ~ (胃 WT) 脳 exp (畏 CL) V = 胃 V 脳 exp (畏 V),). The typical population values of model CL and V were 0.849 L h-1 and 13.7 L, respectively. The evaluation results of goodness of fit, bootstrap and visual test show that the final model is stable and the prediction results are reliable. Conclusion: the established PPK model can describe the pharmacokinetic characteristics of theophylline in elderly patients with chronic obstructive pulmonary disease.
【作者单位】：天津市第五中心医院;北京大学药学院;
【基金】：天津市滨海新区卫生局科技项目(编号:2012BWKY004)
【分类号】：R969.1

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