The effects of captopril and enalapril on digoxin pharmacokinetics in Thai patients with heart failure

Abstract

As concurrent use of digoxin with the ACE inhibitor is common, the effects of captopril and enalapril on the steady-state pharmacokinetics of digoxin in Thai patients with heart failure were studied. Twentyseven patients admitted in Rajvithi Hospital with congestive heart failure (NYHA class 2 and 3) were divided into 3 groups. The digoxin group received digoxin once daily, the enalapril group received digoxin once daily together with enalapril (2.5-10 mg/d) and the captopril group received digoxin once daily together with captopril (25-50 mg/d). Plasma digoxin concentrations were measured at 0,0.5,1,2,3,4,8,12, and 24 hour. Pharmacokinetic parameters were calculated mainly by computer programs. Both captopril and enalapril did not show a significant effect or a suggestive trend for any interaction with steady-state digoxin pharmacokinetics. The mean value of elimination rate constant, distribution rate constant, and absorption rate constant estimated from RSTRIP program were 0.01±0.02, 0,50±0.28, and 1.73±2.43 (/hour) respectively. The correlation of creatinine clearance and digoxin clearance was poor (r=-0.29). The serum digoxin concentration of eight patients (29.63%) were within the therapeutic range (0.8-2.0 ng/ml) while seventeen patients (62.96%) were within the range of 0.5-2.5 ng/ml. predicted trough concentrations were estimated from different pairs of serum digoxin concentrations. The predicted concentrations estimated from two serum concentrations, at about 8 and 12 hour after the last dose, were least difference from the measured values (p=0.68). If only one serum concentration was used for the estimation, the concentration obtained 8 hour was shown to be more accurate than those obtained from 4 or 12 hour. From this study, dosage reduction are not necessary for congestive heart failure patients with normal renal function, concurrently use of digoxin with either captopril or enalapril.