Renal tubular secretion and effects of furosemide

Continuous intravenous infusion of furosemide (8 mg/hr) to 6 healthy subjects induced an average diuresis at steady state of 667 +/- 144 ml/30 min (+/- SD) with a mean plasma concentration of furosemide of 623 +/- 209 ng/ml. The urinary output of Cl- was 50.4 +/- 7.5, of Na+ 47.7 +/- 8.7, and of K+ 5.4 +/- 0.6 mmole/30 min. Intravenous injection of probenecid (1 gm) raised the plasma furosemide level to a maximum of 1,584 +/- 151 ng/ml. Despite this, the urinary excretion of water, Cl-, Na+, and K+ decreased to 52%, 39%, 39%, and 52%, respectively, of control values. Probenecid greatly reduced the urinary excretion and renal clearance of furosemide. There was no or negative correlation between the plasma levels of furosemide and its diuretic and saluretic effects. The urinary excretion and renal clearance of the diuretic correlated positively with these effects. No effect of probenecid on protein binding of furosemide was detected. The findings show that the diuretic effects of furosemide depend on active tubular secretion of the drug and thus on its tubular fluid concentration.