EVALUATION OF POPULATION PHARMACOKINETICS OF ORAL DIGOXIN IN VENOUS PLASMA

Abstract

Objective: Digoxin, a cardiac glycoside with extensive clinical usage, poses challenges due to its narrow therapeutic index and wide interindividual variability. Population pharmacokinetic studies in healthy individuals are scarce despite their importance in understanding drug kinetics. This study aimed to characterize the population pharmacokinetics of oral digoxin in healthy volunteers. Methods: An open-label, single-dose pharmacokinetic study was conducted in 72 healthy Indian adults using digoxin tablets. Plasma samples were collected at various time points, and digoxin concentrations were quantified using Liquid Chromatography-Mass Spectrometry (LC-MS). Population pharmacokinetic analysis was performed using PUMAS® software, incorporating covariates such as creatinine clearance. Results: The two-compartment model best described the data, with a population estimate of clearance (CL/F) of 12.08 l/h in the base model and 8.3 l/h in the final model. Creatinine clearance significantly influenced digoxin clearance. Goodness-of-fit plots indicated model appropriateness, and Monte Carlo simulation validated model performance. Conclusion: This study presents a novel population pharmacokinetic model for oral digoxin in healthy individuals. The model accurately predicts digoxin pharmacokinetics and can guide dosage regimen optimization for better therapeutic outcomes. Further research should explore drug interactions and validate the model in diverse populations.