药代动力学
加药
肾病综合征
分配量
协变量
医学
人口
药理学
养生
分布(数学)
内科学
数学
统计
环境卫生
数学分析
作者
Yiming Zhao,Huan He,Yan-Nan Zang,Libo Zhao,Xiaoling Wang
出处
期刊:International Journal of Clinical Pharmacology and Therapeutics
[Dustri-Verlag Dr. Karl Feistle]
日期:2022-02-01
卷期号:60 (02): 87-96
被引量:2
摘要
The existing cyclosporine (CsA) population pharmacokinetic (PPK) model does not apply well to children. The aim of the study was to establish a CsA PPK model for Chinese children with nephrotic syndrome (NS) and conduct a dosage simulation to provide drug-dosing guidance.A total of 311 drug monitoring data points were collected from 165 children. Blood samples were collected before dosing. Non-linear mixed-effects model was applied to develop the PPK model. Covariate analysis was applied to select candidate factors associated with pharmacokinetic (PK) parameters. A model-based simulation was then performed to estimate the optimal initial dose for different patient subgroups.A one-compartment model with first-order absorption and elimination was chosen to describe the drug trajectory in vivo. The typical values for apparent clearance/absorption fraction (CL/F) and apparent volume of distribution/absorption fraction (V/F) were 40.1/h and 2.32 ×103L, respectively. The covariate analysis revealed that weight and total cholesterol were strongly associated with CL/F and V/F. Goodness-of-fit and model evaluation suggested that the proposed model was acceptable. A dosage regimen table was created for specific pediatric groups to facilitate clinical application.A PPK model of CsA in Chinese pediatrics was successfully established, allowing the development of individualized dosing regimens for Chinese pediatric NS patients.
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