Dosage Optimization of Digoxin in Older Patients with Heart Failure and Chronic Kidney Disease: A Population Pharmacokinetic Analysis.

Abstract

Renal function is an important index for digoxin dose adjustment, especially in patients with chronic kidney disease (CKD). Decreased glomerular filtration rate is common in older patients with cardiovascular disease. The aim of this study was to establish a digoxin population pharmacokinetic model in older patients with heart failure and CKD and to optimize the digoxin dose strategy. Older patients with heart failure and CKD aged > 60years from January 2020 to January 2021 and who had an estimated glomerular filtration rate (eGFR) < 90mL/min/1.73m2 or urine protein production were enrolled in this retrospective study. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using NONMEN software. The precision and stability of the final model were analyzed by graphical and statistical methods. Overall, 269 older patients with heart failure were enrolled. A total of 306 digoxin concentrations were collected, with a median value of 0.98ng/mL (interquartile range [IQR] 0.62-1.61, range 0.04-4.24). The median age was 68years (IQR 64-71, range 60-94) and eGFR was 53.6mL/min/1.73m2 (IQR 38.1-65.2, range 11.4-89.8). A one-compartment model with first-order elimination was developed to describe the digoxin pharmacokinetics. Typical values for clearance and volume of distribution were 2.67L/h and 36.9L, respectively. Dosage simulations were stratified by eGFR and metoprolol. Doses of 62.5 and 125μg were recommended for older patients with eGFR < 60mL/min/1.73m2. A population pharmacokinetic model of digoxin in older patients with heart failure and CKD was established in this study. A novel digoxin dosage strategy was recommended in this vulnerable population.