|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|
|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|
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.
|资助机构||Natural Science foundation of PLA, China|
|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
|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.|