Digoxin and
digoxin immune Fab, its
antidote, are eliminated renally. However, the disposition of Fab in severe
kidney disease is poorly described. Therefore, the disposition of Fab and its relationship to total and free
digoxin were studied in five
digoxin-toxic patients with
end-stage renal disease (n = 4) or severe renal dysfunction (n = 1) with a mean (+/- SD) serum
creatinine of 5.9 +/- 1.2 mg/dl (four patients were receiving long-term
hemodialysis). Serum was drawn after a clinically neutralizing Fab dose (80 to 160 mg) every 12 to 24 hours for 204 to 327 hours. Fab concentrations were assessed by radioimmunoassay, whereas total
digoxin concentrations were assessed with a modified radioimmunoassay or fluorescence polarization immunoassay. The concentration-time profile of Fab appeared to be similar to the concentration-time profile of total
digoxin. The mean (+/- SD) half-lives of the alpha and beta disposition phases of Fab were 13 +/- 5 hours and 96 +/- 31 hours, respectively, which were similar to the alpha and beta parameter estimates of total
digoxin (14 +/- 4 and 123 +/- 16 hours, respectively). Steady-state volume of distribution and systemic clearance of Fab were 0.29 +/- 0.11 L/kg and 0.057 +/- 0.022 ml/min/kg, respectively. Thus, in comparison to values reported in patients with normal renal function, the elimination of Fab and total
digoxin are markedly delayed in patients with
end-stage renal disease, which may necessitate prolonged clinical monitoring.