Abstract
Piretanide is a new loop diuretic similar to furosemide in pharmacologic properties and approximately six times as potent. We gave 3-, 6-, and 12-mg oral doses to 21 normal subjects and collected serial blood and urine samples for assessment of the drug's kinetics and dynamics. There was no evidence for dose-dependent elimination with the doses we used. Peak serum concentrations and urinary excretion rates appeared between 30 and 60 min. Elimination t1/2s were 60 to 90 min. Approximately 45% of a dose was recovered unchanged in the urine. Renal clearance rate was 90 to 100 ml/min and oral clearance was 200 ml/min. Examination of the relationship between urinary excretion rate of piretanide and sodium excretion allowed determination of potency at the tubular level. The piretanide dose that induced half-maximal response was 12.1 +/- 2.6 micrograms/min; it is 69.8 micrograms/min for furosemide and 1 micrograms/min for bumetanide. Piretanide kinetics, therefore, resemble those of furosemide and bumetanide, but piretanide is five or six times as potent as furosemide and one tenth as potent as bumetanide.
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