Clearance of furosemide by the gastrointestinal tract

Approximately 45% of i.v. administered furosemide is eliminated by nonrenal clearance mechanisms. Indirect evidence suggests this might represent intestinal secretion. Therefore, we examined whether the intestinal tract serves as a drug-eliminating organ in man. Intestinal perfusion studies were performed in six healthy volunteers during i.v. furosemide administration (mean serum concentration, 3.74 +/- 0.64 microgram/ml). Subjects were intubated with a multilumen tube which allowed examination of transmucosal water, solute and furosemide movement at separate levels of the gastrointestinal tract. A poorly absorbable electrolyte-mannitol solution was infused in the jejunum (15 ml/min), with polyethylene glycol as a nonabsorbable marker. Furosemide elimination occurred at an equally low rate in all areas of the intestinal tract. Furosemide clearance for the total gastrointestinal tract was 2.1 +/- 0.4 ml/min (mean +/- S.E.M.) compared to a renal clearance of 93.1 +/- 4.6 ml/min. Thus, gastrointestinal elimination amounted to only 2% of renal elimination. The luminal concentration of furosemide in the intestinal tract did not exceed a mean of 0.5 microgram/ml. When the experiments were repeated after administration of probenecid, gut clearance was unchanged but renal clearance was reduced by 70%. In the ileum, furosemide enhanced bicarbonate secretion and induced chloride absorption. We conclude that the intestinal tract contributes only minimally to furosemide elimination in man. From concentration gradients between lumen and plasma and from the fact that probenecid had no effect on elimination rate, it appears likely that active secretion into the intestinal lumen does not occur and that all furosemide appearance in the gut results from passive diffusion.