Evaluation of Digoxin Bioavailability in Single-Dose Studies

Methods for testing digoxin bioavailability were compared in single-dose crossover studies using eight healthy male subjects. Digoxin (0.75 mg) was given by intravenous infusion, intramuscular injection, oral elixir and oral tablet. Multiple serum concentrations and six-day cumulative urinary excretion were determined after each mode of administration. Area under the eight-hour serum concentration curve correlated with cumulative urinary excretion (r = 0.795), but showed greater between-subject variability. First-day and six-day urinary excretion were highly correlated (r = 0.972). After intravenous digoxin, six-day urinary recovery averaged 76 per cent of the dose. Intramuscular digoxin and digoxin elixir were significantly more bioavailable (80 to 83 and 65 to 67 per cent of intravenous) than the tablet (45 to 55 per cent of intravenous), but not sufficiently absorbed to serve as bioavailability standards. Bioavailability of digoxin preparations can be reliably tested by administration of a single 0.75-mg dose to five to eight healthy subjects and comparison of their urinary digoxin excretion over one to six days with that found after one-hour intravenous infusion of the same dose. (N Engl J Med 289:651–654, 1973)