The plasma disposition and renal elimination of digoxin-specific Fab fragments and digoxin in the rabbit.
Administering digoxin-specific antibody fragments (DSFab, 1.9 mg kg-1, i.v.) to rabbits 1 h after digoxin (15 micrograms kg-1 or 12.5 microCi kg-1, i.v.) produced a redistribution of digoxin associated with a 5-fold elevation in total plasma concentration and 36-86% reductions in elimination half-life, apparent volume of distribution at steady-state and total body clearance (CLT). Renal clearance (CLR) was also reduced (54%), but urinary digoxin excretion was increased by one-third (35% vs 25%). This apparent anomaly is due to the large rise in total plasma digoxin concentration with a consequent increase in the area under the plasma concentration curve (AUC). The AUC, which is the denominator term in calculating CLR (and CLT), was increased to a greater extent than urinary digoxin excretion (numerator term in calculating CLR) so that an overall reduction in CLR occurred. The initial presence of digoxin appeared to alter the distribution of DSFab, since their plasma concentrations were markedly higher when the antibody was given after the hapten. The digoxin also reduced (from 3 to 1%) the amount of detectable DSFab in the urine.
Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, UK.
M P
MP
Timsina
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DS
Hewick
D000818:Animals; D004077:Digoxin / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007128:Immunoglobulin Fragments / Q000378:metabolism*; D011817:Rabbits; D014316:Tritium
D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D014316:Tritium; D004077:Digoxin