Population pharmacokinetics of digoxin in Korean patients.
OBJECTIVE
Digoxin possesses a narrow therapeutic index and shows a large inter-patient pharmacokinetic variability. The purpose of this study was to develop a population model for the pharmacokinetics of digoxin in Korean patients.


METHODS
Plasma concentrations of digoxin after multiple administration at varying dosing schedules in Korean patients were used for population modeling. Data analysis was performed with the P-Pharm software. The data were best fitted by a one-compartment model. The effect of demographic and clinical factors like sex, age, weight, disease state, and renal function on the pharmacokinetic parameters of digoxin was investigated.


RESULTS
The study indicated that the clearance of digoxin was influenced by creatinine clearance, while body weight and creatinine clearance were the covariates for its volume of distribution. The population mean estimates for CL and V were 4.4 l/h and 535 l, respectively. Absorption rate constant was lower in females and in the presence of concomitant drug treatment.


CONCLUSIONS
A population pharmacokinetic model for the digoxin pharmacokinetics in a section of Korean patients was developed. The relationships between the pharmacokinetic parameters and the demographic data and the patient-specific covariates were established.
Nagaraja
N V
NV
College of Pharmacy, University of Florida, Gainesville 32610-0494, USA.
Park
Y J
YJ
Jeon
S
S
Sands
C D
CD
Derendorf
H
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000493:pharmacokinetics; D004077:Digoxin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D004077:Digoxin; D003404:Creatinine