Pharmacodynamics and urine pharmacokinetics of three doses of piretanide

Three doses (3 mg, 6 mg and 12 mg) of piretanide, a new high ceiling diuretic, and placebo were given to 8 volunteers to investigate the relationship between the pharmacodynamic parameters, the dose and its urinary excretion. Intake of food and fluid were standardized from 48 h before until 24 h after drug administration. Urinary output, excretion of unchanged drug, and the excretion and clearance of Na+ and K+ were measured hourly for 7 h after treatment. A clear dose-response relationship was found for cumulative urinary output, cumulative excretion of Na+ and K+, clearance of Na+ and K+ and the urinary sodium/potassium ratio. A significant correlation was found between the net urine volume and the excretion of piretanide per time interval. The clearances of Na+ and K+ were significantly correlated with the excretion of piretanide. Clearance values correlated well with corresponding urine volumes.