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Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice
Zhou, Xiao-dan1,2; Gao, Yan1; Guan, Zheng3; Li, Zhong-dong1; Li, Jun2
关键词digoxin population pharmacokinetics aging retrospective studies NONMEM
刊名ACTA PHARMACOLOGICA SINICA
2010-06-01
DOI10.1038/aps.2010.51
31期:6页:753-758
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
资助者Natural Science foundation of PLA, China ; Natural Science foundation of PLA, China
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]TROUGH SCREEN ANALYSIS ; P-GLYCOPROTEIN ; DRUG-INTERACTIONS ; RELATIVE CLEARANCE ; PEDIATRIC-PATIENTS ; JAPANESE PATIENTS ; QUINIDINE ; VERAPAMIL
英文摘要

Aim: To establish a population pharmacokinetic (PPK) model of digoxin in older Chinese patients to provide a reference for individual medication in clinical practice.

Methods: Serum concentrations of digoxin and clinically related data including gender, age, weight (WT), serum creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), albumin (ALB), and co-administration were retrospectively collected from 119 older patients taking digoxin orally for more than 7 d. NONMEM software was used to get PPK parameter values, to set up a final model, and to assess the models in clinical practice.

Results: Spironolactone (SPI), WT, and Cr markedly affected the clearance rate of digoxin. The final model formula is Cl/F=5.9x[1-0.412xSPI] x [1-0.0101 x (WT-62.9)] x [1 -0.0012 x (Cr-126.8)] (L/h); Ka=1.63 (h(-1)); V(d)/F= 550 (L). The population estimates for Cl/F and V(d)/F were 5.9 L/h and 550 L, respectively. The interindividual variabilities (CV) were 49.0% for Cl/F and 94.3% for Vd/F. The residual variability (SD) between observed and predicted

concentrations was 0.365 mu g/L. The difference between the objective function value and the primitive function value was less than 3.84 (P>0.05) by intra-validation. Clinical applications indicated that the percent of difference between the predicted concentrations estimated by the PPK final model and the observed concentrations were -4.3%-+25%. Correlation analysis displayed that there was a linear correlation between observated and predicted values (y=1.35x+0.39, r=0.9639, P<0.0001). Conclusion: The PPK final model of digoxin in older Chinese patients can be established using the NONMEM software, which can be applied in clinical practice.

语种英语
所属项目编号06Ma024
资助者Natural Science foundation of PLA, China ; Natural Science foundation of PLA, China
WOS记录号WOS:000278341900014
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61467
专题北京大学药学院
作者单位1.PLA, Gen Hosp AF, Dept Pharm, Beijing 100142, Peoples R China
2.Anhui Med Univ, Sch Pharm, Hefei 230032, Peoples R China
3.Beijing Univ, Sch Pharm, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhou, Xiao-dan,Gao, Yan,Guan, Zheng,et al. Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice[J]. ACTA PHARMACOLOGICA SINICA,2010,31(6):753-758.
APA Zhou, Xiao-dan,Gao, Yan,Guan, Zheng,Li, Zhong-dong,&Li, Jun.(2010).Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice.ACTA PHARMACOLOGICA SINICA,31(6),753-758.
MLA Zhou, Xiao-dan,et al."Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice".ACTA PHARMACOLOGICA SINICA 31.6(2010):753-758.
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