Comparison of A-49816, a new high-ceiling diuretic, and furosemide in normal volunteers

Abstract

Thirty-six normal male volunteers were entered into this placebo controlled, randomized study of the safety and pharmacologic effects of A-49816, a new high-ceiling diuretic, and furosemide. Following a four-day stabilization period, subjects received placebo, A-49816 (5 mg, 10 mg or 20 mg) or furosemide (20 mg, 40 mg or 80 mg) once daily for seven consecutive days. Urinary excretion of water, sodium and chloride increased following each dose of A-49816 and furosemide. A positive relationship was found between the dose of A-49816 or furosemide and the cumulative sodium excretion at eight hours after dosing on the first treatment day. Mean serum chloride concentration decreased and mean serum bicarbonate and uric acid concentrations increased during administration in most groups receiving A-49816 or furosemide. In conclusion, A-49816 is a diuretic and saluretic agent with 8-hour and 24-hour activity similar to that of furosemide. A-49816 was estimated to be 2.6 times more potent as a saluretic agent than furosemide on the basis of weight.