DISPOSITION OF DIGOXIN IMMUNE FAB IN PATIENTS WITH KIDNEY FAILURE

Digoxin and digoxin immune Fab, its antidote, are eliminated renally. However, the disposition of Fab in severe kidney disease is poorly des cribed. Therefore, the disposition of Fab and its relationship to tota l and free digoxin were studied in five digoxin-toxic patients with en d-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 clinic ally neutralizing Fab dose (80 to 160 mg) every 12 to 24 hours for 204 to 327 hours. Fab concentrations were assessed by radioimmunoassay, w hereas total digoxin concentrations were assessed with a modified radi oimmunoassay or fluorescence polarization immunoassay. The concentrati on-time profile of Fab appeared to be similar to the concentration-tim e 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 h ours, respectively, which were similar to the alpha and beta parameter estimates of total digoxin (14 +/- 4 and 123 +/- 16 hours, respective ly). 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 f unction, the elimination of Fab and total digoxin are markedly delayed in patients with end-stage renal disease, which may necessitate prolo nged clinical monitoring.