Probenecid interferes with the natriuretic action of furosemide

The interaction between probenecid and furosemide was studied in eight hospital patients (ages 20-65 years) who had been treated with oral furosemide, 40 mg daily, and moderate salt restriction for 10 days or longer. After stabilization of drug therapy and diet for at least 3 days, probenecid, 0.5 g twice a day, was given for 3 days and then discontinued. The 24-h urinary sodium excretion (UNaV) significantly decreased from 56.3 +/- 7.2 to 35.9 +/- 7.1 mmol/day when probenecid was added to the treatment regimen (p less than 0.01), and then significantly increased to 61.7 +/- 10.3 mmol/day after probenecid was discontinued (p less than 0.01). Parallel with the changes in UNaV, there were also significant corresponding changes (p less than 0.01) in urinary excretion of uric acid (392.4 +/- 46.5, 600.9 +/- 102.1, and 345.0 +/- 33.2 mg/day, respectively), renal clearance of uric acid (3.7 +/- 0.3, 14.3 +/- 2.4, and 4.1 +/- 0.3 ml/h/kg, respectively), and serum uric acid concentration (7.7 +/- 0.5, 3.3 +/- 0.2, and 6.3 +/- 0.3 mg/dl, respectively). Before and after discontinuing probenecid therapy, there were no significant differences in these parameters (p greater than 0.05). In conclusion, the natriuretic action of furosemide was attenuated by concurrent probenecid therapy, probably owing to a reduction of furosemide delivery to the luminal side of renal tubules.