Diuretic effect and metabolism of bumetanide in man.

Bumetanide (3-N-butylamino-4-phenoxy-5-sulfamyl-benzoic acid) is a sulfonamide congener with potent diuretic activity in man. Oral administration of 14C-bumetanide (2 mg, 22 71Ci) to 4 adult male volunteers was rapidly and almost completely absorbed (greater than 95%). Its average apparent volume of distribution was 25 L. Bumetanide induced a ceiling diuresis at 1 hr, with loss of Na+ and water for 4 to 5 hr. Loss of K+ was minimal. Bumetanide was quickly eliminated by metabolism and urinary excretion with a plasma half-life of 1.5 hr. The administered radioactivity was almost completely recovered (96%), 81% appearing in the urine and the remainder in the feces. In one subject with bilary T tube, 14.4% of the dose was excreted in the bile which suggested that the radioactivity of the feces came from the bile. Thin-layer chromatography analysis of pooled urine, bile, and fecal samples showed the elimination of bumetanide could be explained by excretion of unchanged drug and side chain oxidative metabolism and conjugation.