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Kinetic and dynamic comparison of piretanide and furosemide
Author(s) -
Lawrence J. R.,
Ansari A. F.,
Elliott H. L.,
Sumner D. J.,
Brunton G. F.,
Whiting B.,
Whitesmith R.
Publication year - 1978
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1978235558
Subject(s) - furosemide , diuretic , chemistry , natriuresis , endocrinology , pharmacology , excretion , medicine , urine
In a comparative study with the use of a randomized crossover design, piretanide, a new “loop” diuretic, was given intravenously to 8 normal volunteers. Following the injection of radioiodinated human serum albumin to allow assessment of plasma volume changes, subjects were submaximally water loaded to facilitate urine collection for a period of 210 min after the intravenous injection of 12 mg piretanide, 40 mg furosemide, and placebo. Plasma piretanide concentrations, measured by a sensitive spectrofluorimetric assay, declined biexpoentially after intravenous bolus injection. The mean total body clearance was 246 ± 52 ml min −1 and the mean renal clearance was 136 ± 61 ml min −1 . Significant increase in urine flow, natriuresis, and kaliuresis were evident within 15 min of piretanide injection and persisted for 90 min. A calciuric effect was also observed over this period. While a uricosuric action was observed during the first 15 min the overall effect was urate retention which became evident between 45 and 150 min. In none of these measured effects did 12 mg piretanide differ from 40 mg furosemide. Plasma volume declined linearly from the time of drug injection, a variable plateau being reached at approximately 90 min. From 15 min after injection, individual subjects showed a good linear correlation between the piretanide or furosemide urinary excretion rate and the concomitant sodium or potassium excretion rate. Corresponding concentration‐effect regression lines showed no important differences between the two diuretics. The relative potency of the drugs (piretanide : furosemide) for sodium excretion was 2.42: 1. For both piretanide and furosemide the time course of diuretic effect closely paralleled the extrapolated amount of drug in the peripheral compartment of the proposed open 2‐compartment model.