Population pharmacokinetic model of digoxin in older Chinese patients and its application in clinical practice.
OBJECTIVE
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[1-0.412 x SPI] x [1-0.0101x(WT-62.9)] x [1-0.0012x(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 V(d)/F. The residual variability (SD) between observed and predicted concentrations was 0.365 microg/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 observed and predicted values (y=1.35x+0.39, r=0.9639, P<0.0001).


CONCLUSIONS
The PPK final model of digoxin in older Chinese patients can be established using the NONMEM software, which can be applied in clinical practice.
Department of Pharmacy, General Hospital of Air Force, PLA, Beijing, China.
Xiao-dan
XD
Zhou
Yan
Y
Gao
Zheng
Z
Guan
Zhong-dong
ZD
Li
Jun
J
Li
D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People; D003198:Computer Simulation; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D012044:Regression Analysis; D012189:Retrospective Studies; D012984:Software
D000889:Anti-Arrhythmia Agents; D004077:Digoxin