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.