The influence of nonsteroidal anti‐inflammatory drugs and probenecid on the renal response to and kinetics of piretanide in man

The mechanism by which nonsteroidal antiinflammatory drugs interfere with the action of loop diuretics is not clear. We studied the renal response to an acute challenge of piretanide superimposed on pretreatment with either placebo, probenecid, indomethacin, or piroxicam in seven maximally hydrated subjects. No change was seen in glomerular filtration rate, as measured by creatinine clearance, throughout the experiments. When compared with responses to piretanide challenge after placebo pretreatment, probenecid reduced by 65% the peak fractional excretion of sodium (FENa), with a corresponding reduction in diuretic excretion. Pretreatment with indomethacin reduced peak FENa by 35%, but urinary delivery of piretanide was not altered. In contrast, piroxicam did not influence FENa but significantly reduced the delivery of both sodium and piretanide into urine. We conclude that the activity of nonsteroidal antiinflammatory drugs within the renal tubule varies among individual drugs and cannot be explained solely by their common mechanism of antiinflammatory action. Clinical Pharmacology and Therapeutics (1988) 44, 531–539; doi:10.1038/clpt.1988.190