Piretanide 60 mg was administered intravenously over 30 min to 15 men with different degrees of
renal failure. The mean
piretanide serum concentration at the end of the infusion period was 5.72 +/- 1.51 micrograms/ml. Serum
piretanide concentration-time curves declined biexponentially and 24 hours after medication the serum level had fallen to less than twice the detection limit. The terminal half-life ranged from 1.63 to 3.44 h. A relationship to
creatinine clearance was not demonstrable. The mean metabolic clearance of
piretanide was 107.7 +/- 47.6 ml/min/1.73 m2 body surface area and was the same as that reported for healthy subjects. The renal clearance of
piretanide ranged from 3.33 to 43.9 ml/min/1.73 m2 body surface area and very closely correlated with the
creatinine clearance (p less than 0.01). Its renal clearance depended principally on active secretion of the drug into the tubule, and glomerular filtration appeared unimportant. There was a close relationship between the amount of
piretanide excreted in the urine and the
creatinine clearance. Because the diuretic effect of
piretanide depends on the concentration of the drug in the tubule, the observed correlation might be of use in evaluating the appropriate dosage of
piretanide in patients with
renal failure. The present data suggest that single daily doses of
piretanide will not result in accumulation, even when high doses are administered to patients with advanced
renal failure.