We evaluated the effect of quinidine on digoxin pharmacokinetics in six patients with severe renal failure. Quinidine reduced the total body clearance of digoxin from 1.87 to 1.06 1/hour (p < 0.001), and prolonged the digoxin half-life of elimination from 5.20 to 9.61 days (p < 0.01). The digoxin volume of distribution was unchanged. Renal clearance of digoxin was negligible; thus, the decrease in total body clearance was due to a decrease in the nonrenal clearance of digoxin. The mean trough

more »

... rum concentrations of quinidine ranged from 1.0 to 3.0 ,ug/ml. We conclude that in patients with chronic renal failure, the dose of digoxin should be decreased by 50% if quinidine therapy is initiated. Analytical Methods Digoxin serum concentrations were determined using the Becton-Dickinson '251 radioimmunoassay, with the following modifications. Standard solutions of digoxin (Boehringer-Mannheim) were diluted in pooled human plasma and a standard curve (range 0-4 ng/ml) was prepared for each assay. All samples and standards were run in duplicate. The charcoal suspension contained 0.15 M NaCl, 3.6 mM sodium barbital, 3.6 mM sodium acetate, 0.03% dextran T-80, and 1.25% Norit-A activated charcoal pH 7.2. After cen-by guest on