Digitoxin accumulation.

1 Nine healthy volunteers received single 1 mg intravenous doses of digitoxin, following which serum digitoxin concentrations were measured at multiple points in time over the next 14 days. 2 Mean kinetic variables for digitoxin were: volume of distribution, 0.76 l/kg; elimination half‐life, 8 days; total clearance, 0.049 ml min‐1 kg‐1. 3 After a drug‐free interval of at least 4 months, subjects took 0.07 mg of oral digitoxin daily for 28 consecutive days. Serum digitoxin concentrations were measured during the period of dosage and in the 21 day post‐dosage washout. 4 Digitoxin accumulation was slow, proceeding with a mean half‐life (7.9 days) that was nearly identical to the single‐dose half‐life. However, the two were not significantly correlated. 5 Mean observed steady‐state serum concentrations (15.4 ng/ml) also were nearly identical to those predicted from the single‐ dose study (15.3 ng/ml), but again the two were not significantly correlated. 6 Steady state is very slowly attained after initiation of maintenance therapy with digitoxin. The kinetic data suggest that a loading dose on the average should be 12 times the maintenance dose.