Therapeutic Drug Monitoring and Population Pharmacokinetics of Digoxin in Jordanian Patients

Abstract

Therapeutic monitoring of digoxin and the population pharmacokinetic parameters in Jordanian patients were done. Fifty three patients visited cardiac department of Jordan University hospital participated in this study, thirty two patients had congestive heart failure (CHF), while twenty one patients had atrial fibrillation (AF). Ninety three blood samples were collected from those patients for the measurement of digoxin level using AxSYM digoxin II assay method. Serum creatinine and potassium levels were also measured, in addition to blood pressure and heart rate. Microsoft Excel and Statistica programs were used for kinetic and statistical analysis. NONMEM computer program ADVAN 4 and 2 compartment model was used for population analysis of digoxin parameters. The serum digoxin level ranged from 0.11-4 ng/ml. The percentage of all patients enrolled in this study that were out of therapeutic range was 49.05%. Serum digoxin levels were out of therapeutic range in 53.12% of patients with CHF and 42.85% in those with AF. The pharmacokinetic parameters for digoxin obtained in this study using traditional methods were: creatinine clearance CLcr (89.78 ± 45.61 ml/min), digoxin actual clearance CL (200.57 ± 154.52 L/day), volume of distribution V (541.57 ± 149.87L), t1/2(2.98 ± 2.05 day), elimination rate constant (0.41± 0.396 day-1). A strong correlation was also found between actual digoxin clearance with log dose normalized (R2=0.999), and t1/2 (R2= 0.875). No correlations were found between the log of the normalized dose and other pharmacokinetic parameters or potassium levels. The population pharmacokinetic parameter for digoxin obtained in this study were: CL (3.34L/h), Vc (3.27L), Vt (123L), inter-compartment clearance Q (72L/h), absorption rate constant KA (1.25h-1). In Jordanian patients with either AF or CHF digoxin dose adjustment based on therapeutic drug monitoring principles is recommended. Digoxin pharmacokinetics were similar to those reported in non-Jordanian patients; estimated population pharmacokinetic parameters were in agreement with literature values.