Digoxin-specific Fab fragments impair renal function in the rat.
The effect on renal function, and the plasma and urinary disposition, of digoxin-specific antibody fragments (DSFab), were studied using the rat as an experimental model. After 24h, DSFab (2 mg kg-1, i.v.) caused decreases in urine volume and creatinine clearance of 34 and 33%, respectively, when measured in the same rats. However, only the creatinine clearance was significantly changed when compared with a separate saline-treated control group. Plasma and urinary creatinine concentrations were unaffected by DSFab treatment. Since creatinine clearance approximates to glomerular filtration rate (GFR), it appears that a dose of DSFab equivalent to about one-fifth of the usual clinical dose, causes a reduction in GFR of about one-third. In patients undergoing digitalis therapy, a degree of renal impairment is common and it is possible that this may be exacerbated by treatment with DSFab. DSFab had an elimination half-life of 178 min, an apparent volume of distribution (Vd) of 106 mL kg-1 and a plasma clearance of 0.42 mL kg-1 min-1. If it is assumed that the plasma volume of a rat is approximately 35 mL kg-1, the measured Vd suggests appreciable penetration of DSFab into the extracellular fluid at this dose. Seventy-two hours after injection, only 7.6% of the administered dose of DSFab was found in the urine.
Moran
R J
RJ
Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital, UK.
Struthers
A D
AD
Hewick
D S
DS
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects* / Q000652:urine; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine
D007140:Immunoglobulin Fab Fragments; C050199:digoxin antibodies Fab fragments; D003404:Creatinine