Acute effects of piretanide in normal subjects.

Acute clearance studies were performed in normal subjects to assess the actions of the new diuretic, piretanide, on renal function. The drug increased both glomerular filtration rate and effective renal plasma flow in roughly proportionate amounts, so that filtration fraction did not change. In a dosage of 2 to 3 mg, it induced an increase in sodium excretion of almost 13% of filtered load, and there was an associated 2- to 3-fold increase in potassium excretion. The abstraction of solute-free water from the collecting duct was markedly reduced, but the drug induced no significant decline in the generation of free water. The rate of bicarbonate excretion, as well as that of titratable acid and ammonium, was increased approximately proportionately so that there was no increase in urinary pH or net hydrogen ion excretion. There was no phosphaturia, a unique finding, since all other drugs and maneuvers that cause a bicarbonate diuresis are also phosphaturic. Piretanide increased calcium excretion by approximately 19% of filtered load. The data suggest that the drug acts largely in the ascending limb of the loop of Henle and that it also affects the proximal tubule. Despite its sulfonamide structure, none of the drug's effects appear to be related to inhibition of carbonic anhydrase.