Digoxin-specific Fab fragments impair renal function in the rat

J Pharm Pharmacol. 1994 Oct;46(10):854-6. doi: 10.1111/j.2042-7158.1994.tb03743.x.

Abstract

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.

MeSH terms

  • Animals
  • Creatinine / metabolism
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects*
  • Immunoglobulin Fab Fragments / urine
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / physiopathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Urine

Substances

  • Immunoglobulin Fab Fragments
  • digoxin antibodies Fab fragments
  • Creatinine