Multiple-dose kinetics of digoxin were studied over a 7-day period in five neonates receiving intravenous digoxin therapy (one initial digitalizing dose followed by single daily doses). Their weights ranged from 1.04 to 2.68 kg (means = 1.61 kg), gestational ages from 28 to 39 weeks (means = 31.8 weeks), and postnatal ages from 2 to 19 days (means = 8.0 days). The 24-hour serum digoxin levels and urinary creatinine and digoxin excretion after the 1st and 7th doses on days 1 and 7 were employed to derive the kinetic parameters. Values of each following parameter (mean +/- SD) were obtained on days 1 and 7, respectively: (1) creatinine clearance (ml/min/1.73 m2) 12 +/- 6, 13 +/- 8; (2) renal digoxin clearance (ml/min/1.73 m2) 13 +/- 8, 15 +/- 10; (3) total body digoxin clearance (ml/min/1.73 m2) 35 +/- 14, 39 +/- 24; (4) volume of distribution (L/kg) 7.2 +/- 1.0, 6.9 +/- 1.1; and (5) half-life (hours) 48 +/- 19, 49 +/- 27. No consistent changes of the above kinetic parameters from days 1 to 7 were observed in these five neonates (P greater than 0.05, paired student's t-test).