To explore a possible interaction between digoxin and verapamil, a single‐dose kinetic study of digoxin was performed and then repeated after 10 days of verapamil treatment in eight healthy subjects. Verapamil diminished the apparent central distribution volume of digoxin from 0.83 ± 0.25 to 0.64 ± 0.17 l/kg (P < 0.05) and reduced total body clearance of digoxin from 3.28 ± 0.58 to 2.15 ± 0.66 ml/min/kg (P < 0.001) by impairing both renal and extrarenal clearance. Biological digoxin half‐life rose from 38.6 ± 8.5 to 50.5 ± 8.3 hr (P < 0.005). Reduction of renal clearance of digoxin may be due to inhibition of tubular secretion. The underlying mechanisms of extrarenal interaction are not known, but impaired hepatic degradation of digoxin induced by verapamil should be considered. Clinical Pharmacology and Therapeutics (1981) 30, 311–316; doi:

To evaluate the possible effect of quinidine on digoxin bioavailability, the steady state digoxin kinetics was examined with and without concomitant quinidine therapy, in 7 cardiac patients after simultaneous administration of oral digoxin and intravenous [3H]-digoxin. In the presence of quinidine, the absorption rate constant of digoxin (ka) increased from 2.72 +/- 1.04 to 3.53 +/- 1.34 h-1 (p less than 0.05), whereas lag time and peak time decreased from 0.16 +/- 0.10 to 0.05 +/- 0.04 h (p less than 0.05) and from 0.92 +/- 0.27 to 0.69 +/- 0.19 h (p less than 0.02), respectively. Predose plasma digoxin increased from 0.41 +/- 0.25 to 0.70 +/- 0.31 ng/ml (p less than 0.02), while peak plasma digoxin increased from 0.93 +/- 0.34 to 1.63 +/- 0.46 ng/ml (p less than 0.02). The systemic availability of digoxin increased from 68.48 +/- 13.35 to 79.09 +/- 14.89% (p less than 0.05) in the presence of quinidine. Quinidine had no effect on the biotransformation pattern of digoxin, as assessed by thin layer chromatography. Quinidine increases the rate and extent of digoxin absorption, and this interaction contributes significantly to the elevation in plasma digoxin during both its distribution and elimination phases.