丙戊酸致癫痫患者血氨升高的群体药效学分析
发布时间：2018-07-14 08:55
【摘要】：目的:建立群体药效学(PPD)模型考察丙戊酸(VPA)致癫痫患者血氨升高的量-效关系,以促进安全用药。方法:搜索提取已发表的研究资料,以患者VPA血浆药物浓度作为药动学指标,血氨浓度作为药效学指标,采用非线性混合效应建模进行数据分析。药效学结构模型选用Sigmoid-Emax模型。用拟合优度、自举法和直观预测检验对模型的预测性能进行内部验证。用未参与建模的数据对模型进行外部验证。结果:PPD模型参数的群体典型值分别为:E0(基线效应值)=25.09μg·dL~(-1),EC50(达最大效应一半时效应室浓度)=107.26 mg·L~(-1),γ(陡度因子)=4.00,Emax(最大效应参数)=471.95μg·dL~(-1)。内部验证和外部验证结果表明最终模型稳定,预测结果可靠。结论:本研究成功建立了能够反映患者丙戊酸血药浓度与血氨水平之间定量关系的PPD模型,可为临床安全用药提供参考。
[Abstract]:Aim: to establish a population pharmacodynamics (PPD) model to investigate the dose-effect relationship of elevated blood ammonia in patients with epilepsy induced by valproic acid (VPA) in order to promote safe drug use. Methods: the published data were searched and extracted. The plasma concentration of VPA was used as the pharmacokinetic index and the concentration of blood ammonia as the pharmacodynamics index. The data were analyzed by nonlinear mixed effect modeling. Sigmoid-Emax model was used for pharmacodynamics structure model. The predication performance of the model is verified by the goodness of fit, bootstrap method and visual prediction test. External validation of the model with non-participating modeling data. Results the typical population values of the weight PPD model parameters were: 1: E0 (baseline effect value) 25.09 渭 g dL-1) EC50 (maximum effect half time) 107.26 mg L-1, 纬 (steepness factor) 4.00 渭 g dLmax (maximum effect parameter) 471.95 渭 g dL ~ (-1). The results of internal and external verification show that the final model is stable and the prediction results are reliable. Conclusion: this study successfully established a PPD model which can reflect the quantitative relationship between serum valproic acid concentration and blood ammonia level in patients with valproic acid.
【作者单位】： 武汉市妇女儿童医疗保健中心;武钢第二职工医院;
【基金】：2016年度武汉市卫生计生科研基金资助项目(编号:WX16B18)
【分类号】：R742.1
，
本文编号：2121131
[Abstract]:Aim: to establish a population pharmacodynamics (PPD) model to investigate the dose-effect relationship of elevated blood ammonia in patients with epilepsy induced by valproic acid (VPA) in order to promote safe drug use. Methods: the published data were searched and extracted. The plasma concentration of VPA was used as the pharmacokinetic index and the concentration of blood ammonia as the pharmacodynamics index. The data were analyzed by nonlinear mixed effect modeling. Sigmoid-Emax model was used for pharmacodynamics structure model. The predication performance of the model is verified by the goodness of fit, bootstrap method and visual prediction test. External validation of the model with non-participating modeling data. Results the typical population values of the weight PPD model parameters were: 1: E0 (baseline effect value) 25.09 渭 g dL-1) EC50 (maximum effect half time) 107.26 mg L-1, 纬 (steepness factor) 4.00 渭 g dLmax (maximum effect parameter) 471.95 渭 g dL ~ (-1). The results of internal and external verification show that the final model is stable and the prediction results are reliable. Conclusion: this study successfully established a PPD model which can reflect the quantitative relationship between serum valproic acid concentration and blood ammonia level in patients with valproic acid.
【作者单位】： 武汉市妇女儿童医疗保健中心;武钢第二职工医院;
【基金】：2016年度武汉市卫生计生科研基金资助项目(编号:WX16B18)
【分类号】：R742.1
，
本文编号：2121131
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