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Spironolactone. I. Disposition and metabolism
Author(s) -
Karim A.,
Zagarella J.,
Hribar J.,
Dooley M.
Publication year - 1976
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/cpt1976192158
Subject(s) - metabolite , urine , glucuronide , chemistry , spironolactone , metabolism , endocrinology , pharmacokinetics , medicine , excretion , pharmacology , biochemistry , aldosterone
This study describes absorption, excretion, and metabolism of [20− 3 H]‐spironolactone (SP) in 5 healthy men. After a single oral dose (200 mg + 200 p,Ci) of the drug given in alcoholic solution, the peak serum levels of the ethyl acetate‐extractable tritium and the dethioacetylated metabolite canrenone were 763 ± 400 ng/ml (mean ± SD) and 415 ± 145 ng/ml, respectively. These levels occurred within 3 hr. The serum half‐life (T ½ ) of the extractable materials was 37.3 ± 6.53 hr. Canrenone levels declined in two phases. The Tdrom 2.5 to 12 hr was 4.42 ± 1.07 hrandfrom 12 to 72 hr was 16.8 ± 2.75 hr. In the blood both SP and canrenone were confined largely in the plasma, and their protein binding exceeded 89% at concentrations of 550 and 710 ng/ml, respectively. In 5 days 31.6 ± 5.87% of the radioactivity was excreted in the urine and 22.7 ± 14.1% in the feces. Unchanged SP was not detected in the urine. The major urinary metabolites were canrenone (5.04 ± 2.83% of dose), 6ß‐OH‐sulfoxide (5.21 ± 0.93% of dose), and canrenoate ester glucuronide (6.2% of dose).