Enhancement of digoxin clearance by mannitol diuresis: in vivo studies and their clinical implications

Because of its narrow margin of safety, digoxin toxicity may occur even during routinely prescribed doses. Due to its very large distribution volume (10 L/kg), only less than 1% of the body load is available for removal, making hemodialysis and hemoperfusion ineffective. Until recently it was assumed that most of the body load of digoxin is eliminated by glomerular filtration. It is now evident that substantial tubular reabsorption and secretion take place. As for the other drugs which are reabsorbed by the tubule (eg Aspirin), we wished to assess whether urine flow rate affect digoxin renal clearance. We studied anesthetized, ventilated dogs. They were preloaded with 25 micrograms/kg IV digoxin the day prior to the experiment. The dogs were infused initially with saline and after a urine collection for digoxin renal clearance 200 ml 10% mannitol were infused over 30 minutes. Digoxin renal clearance was increased 2-3 folds in all cases with a small increase in inulin clearance. Based on these results, the ability of mannitol diuresis to remove significant systemic amounts of digoxin should be tested in acute toxicity in animals. This may be an adjunct modality to FAB antibodies and activated charcoal.