Population pharmacokinetics of oral digoxin in venous plasma samples of healthy volunteers: Population pharmacokinetics of digoxin

Sirajudeen Mahaboob; Arun KP; SD Rajendran; GNK Ganesh

doi:10.22159/ijap.2024v16i5.51291

Authors

Sirajudeen Mahaboob Research Scholar, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Tamil Nadu, India
Arun KP Vice Principal, Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Tamil Nadu, India.
SD Rajendran Director, Scitus Pharma Services Pvt. Ltd., DRR Avenue, 2nd Cross St, Audco Nagar, Kattupakkam, Chennai, India.
GNK Ganesh Associate Professor, Department of Pharmaceutics, JSS College of Pharmacy, JSSAHER, Ooty, Tamilnadu, India

DOI:

https://doi.org/10.22159/ijap.2024v16i5.51291

Keywords:

Digoxin, population pharmacokinetics, healthy volunteers, two-compartment model, LC-MS, PUMAS®, dosage optimization

Abstract

ABSTRACT

Background and Objectives: 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 Cardioxin tablets. Plasma samples were collected at various time points, and digoxin concentrations were quantified using 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.