Effects of piretanide in normal subjects.
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.
D000042:Absorption; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D013449:Sulfonamides / Q000378:metabolism*
D013449:Sulfonamides; C015451:piretanide