Pharmacokinetics of spironolactone in man.
Five healthy male volunteers received 500 mg Aldactone orally together 100 muCi 3H-20-21-spironolactone; one elderly patient received 1 mCi 3H-spironolactone without additional 'cold' drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25-40 min after administration amounting to 2-3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t 1/2: 2.57 +/- 0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t 1/2: 1.66 +/- 0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47-57% of the dose were excreted in urine and the remaining amount could be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t 1/2: 0.9 +/- 0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7 alpha-methylsulfonyl-6 beta, 17 beta-dihydroxy-4-androsten-17 alpha-yl) propionic acid gamma-lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6 beta-OH-7 alpha-methylsulfinyl-spirolactone leveled off and seemed to be and endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001711:Biotransformation; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D005470:Fluorometry; D006801:Humans; D007700:Kinetics; D008297:Male; D013148:Spironolactone / Q000097:blood / Q000378:metabolism* / Q000652:urine; D013997:Time Factors
D013148:Spironolactone