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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
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
WOS记录号WOS:000278341900014
项目编号06Ma024
资助机构Natural Science foundation of PLA, China
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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