The effect of captopril on pharmacokinetics of digoxin in patients with mild congestive heart failure.

The effect of captopril on steady-state pharmacokinetics of digoxin was studied in 12 patients with mild congestive heart failure (CHF; New York Heart Association functional class 1 or 2). Serum and urine digoxin concentrations were determined before and after a repeated administration of captopril in the patients on chronic digoxin therapy. The patients were taking digoxin, 0.25-0.375 mg/day, once daily, and were concurrently administered captopril, 37.5 mg/day, three times daily, for seven days. Peak serum concentration of digoxin (SCD) before and after captopril was 2.1 +/- 0.2, mean +/- SEM, and 2.0 +/- 0.1 ng/ml; the time to peak was 1.1 +/- 0.2 and 1.8 +/- 0.3 h; the terminal half-life (t1/2 alpha) was 10.9 +/- 1.0 and 8.7 +/- 0.9 h, and the area under the concentration-time curve to 24 h was 26.9 +/- 2.4 and 27.6 +/- 2.0 ng.h/ml. There was no significant difference between patients without and with captopril in SCD and its pharmacokinetic parameters. Renal digoxin clearance and creatinine clearance also showed no significant difference. After an administration of captopril, angiotensin-converting-enzyme (ACE) activity was well suppressed. These results suggest that captopril does not increase SCD in patients with CHF, and effectively suppresses ACE activity. Thus, modification in the dosage regimen of digoxin may be unnecessary in the case of coadministration with captopril.