Efficacy and pharmacokinetics of piretanide in patients with congestive heart failure

The efficacy and pharmacokinetics of the diuretic piretanide were studied in two groups of six patients hospitalized for congestive heart failure. A dosage of 2 x 6 mg day-1 to 2 x 12 mg day-1 of intravenous piretanide for 7 days was sufficient to abrogate most symptoms of cardiac insufficiency. When compared with another group of healthy volunteers, patients with congestive heart failure had reduced total body clearance of piretanide of about 50% which was attributable to a diminished renal but not non-renal clearance. The analysis of the interrelationship between urinary piretanide excretion and diuresis by means of a linearized Emax-model revealed a maximal diuresis of 231 ml h-1 and a urinary piretanide excretion to induce half-maximal diuresis of 245 micrograms h-1. Thus patients with congestive heart failure exhibit a decreased renal clearance of piretanide and a good response to this high ceiling diuretic after intravenous dosing.