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Disposition of digoxin immune fab in patients with kidney failure
Author(s) -
Ujhelyi Michael R,
Robert Sylvie,
Cummings Doyle M,
Colucci Robert D,
Sailstad Jeffrey M,
Vlasses Peter H,
Findlay John W A,
Zarowitz Barbara J
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.165
Subject(s) - digoxin , radioimmunoassay , volume of distribution , medicine , renal function , creatinine , pharmacokinetics , hemodialysis , pharmacology , urology , endocrinology , heart failure
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 α and β disposition phases of Fab were 13 ± 5 hours and 96 ± 31 hours, respectively, which were similar to the α and β 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.