Single- and multiple-dose kinetics of intravenous digoxin.

Nine healthy men received 0.5, 1.0, and 1.5 mg digoxin intravenously in random sequence on occasions separated by at least 4 wk. Digoxin concentrations were measured in serum samples drawn during 36 hr after each dose, and a mean across-dose kinetic profile was determined for each subject. After a 6-mo washout period, the same subjects received 0.25 mg digoxin intravenously every 24 hr for 10 consecutive days. Samples were drawn every 12 hr during the first 9 days and at multiple points during 72 hr after the last dose. Mean kinetic variables for the single- and multiple-dose trials were as follows: elimination half-life (t1/2), 27.9 and 38.0 hr (r = 0.62); volume of distribution, 5.5 and 7.4 l/kg (r = -0.56); total clearance, 2.50 and 2.49 ml/min/kg (r = 0.19); urinary excretion t1/2, 40.9 and 37.9 hr (r = -0.14). Mean observed and predicted predose steady-state serum concentrations were 0.59 and 0.79 ng/ml (r = -0.02). Mean values of accumulation and elimination t1/2 were nearly identical (27.8 and 27.9 hr), but were not positively correlated (r = -0.64). Multiple-dose digoxin therapy leads to no systematic change in digoxin clearance. Single-dose kinetics is poorly predictive of the rate and extent of drug accumulation and of washout kinetics during and after multiple-dose therapy.