Analysis of the natriuretic action of a loop diuretic, piretanide, in man

1. The renal responses to a loop diuretic, piretanide, were investigated in a group of fourteen healthy volunteers. The effect of fluid replacement on the drug-response relationship was evaluated in the absence and in the presence of probenecid pretreatment following both oral and intravenous administration of piretanide. 2. Urinary excretion of piretanide was greater when volume losses were replaced than in the absence of volume replacement (i.v. dose: 3.32 +/- 0.15 vs 2.55 +/- 0.23 mg 6 h-1, P less than 0.01; oral dose: 2.57 +/- 0.09 vs 1.87 +/- 0.27 mg 6 h-1, P less than 0.01). With intravenous piretanide urinary excretion of sodium was likewise greater in the fluid replaced group (198 +/- 4 vs 141 +/- 10 mmol 6 h-1, P less than 0.01); these differences caused by fluid replacement did not however occur after oral dosing of piretanide (181 +/- 12 vs 167 +/- 14 mmol 6 h-1). 3. Probenecid pretreatment significantly decreased the renal excretion of piretanide in all subjects and consistently decreased the natriuretic response with the exception of intravenous piretanide challenge in subjects not undergoing fluid replacement. In this situation, despite probenecid causing a decrease in the amount of drug excreted (2.55 +/- 0.23 vs 1.63 +/- 0.15 mg 6 h-1, P less than 0.05) the sodium output was unaltered (141 +/- 10 vs 152 +/- 16 mmol 6 h-1, NS). 4. Complete replacement of the induced fluid losses resulted in the enhancement of the renal response, without affecting the shape of the diuretic response curve, of either the intravenous or orally administered piretanide.(ABSTRACT TRUNCATED AT 250 WORDS)