Population pharmacokinetics of digoxin in Thai pediatric patients.
OBJECTIVE
To determine the digoxin population pharmacokinetic parameters and influence of various factors on pharmacokinetic parameters in Thai pediatric patients with heart disease.


METHODS
The present study was an analytical cross-sectional study design and population pharmacokinetic modeling study. The data of 130 patients and 264 samples with an age range of 0.1-15.7-years-old were collected during routine care. Blood samples were drawn at various times after administration. All patients received digoxin administration with a dose ranged of 1.7-13.6 microg/kg/day at Queen Sirikit Heart Center; Khon Kaen University, Thailand. Population pharmacokinetic modeling was developed from digoxin data by using NONMEM program (Version V) according to one-compartment of subroutine ADVAN2 TRANS2 model.


RESULTS
Weight, age, height and the presence of congestive heart failure (CHF) were significant covariates on CL. Weight and the presence of CHF were significant covariates on Vd. The final population model of CL and Vd in pediatric patients were as follows: CL/F (L/h) for infant (0-1 year) = 0.322 * WT (kg); CL/F (L/h) for children (> 1 year) = (0.138 * WT(kg) + 0.0319 * HT (cm) * 0.765CHF; and Vd/F (L) for all ages = 9.27 * WT (kg) * 1.75CHF. The interindividual variability of CL/F, Vd/F and intraindividual variability with proportional error model were 31.48, 35.56, and 41.7%, respectively. In the validation data set (57 samples), predictive performance in terms of bias (ME) and precision (RMSE) were -0.049 ng/mL (95% CI: -0.118-0.020) and 0.269 ng/mL (95% CI: 0.216-0.312), respectively.


CONCLUSIONS
This simple final population model of Vd and CL can be used in clinical practice for estimating appropriate dosage regimen of loading dose and maintenance dose, respectively. Current weight, height, and presence of CHF should be taken into account when designing dosage regimen for individualized pediatric patients.
Preechagoon
Yupaporn
Y
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand. yuppre@kku.ac.th
Somsaard
Peeraya
P
Petcharattana
Setthasiri
S
D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004077:Digoxin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006330:Heart Defects, Congenital / Q000188:drug therapy*; D006801:Humans; D008297:Male; D015233:Models, Statistical; D013785:Thailand
D000889:Anti-Arrhythmia Agents; D004077:Digoxin