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Pharmacokinetics of spironolactone in man

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Summary

Five healthy male volunteers received 500 mg Aldactone® orally together with 100 μCi 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 culd 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-7α-methylsulfonyl-6β, 17β-dihydroxy-4-androsten-17α-yl) propionic acid γ-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 6β-OH-7α-methylsulfinylspirolactone leveled off and seemed to be an endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.

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Authors and Affiliations

  1. Institut für Klinische Pharmakologie und Medizinische Klinik und Poliklinik, Klinikum Steglitz der Freien Universität Berlin, Hindenburgdamm 30, D-1000, Berlin 45

    U. Abshagen, H. Rennekamp & G. Luszpinski

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  1. U. Abshagen
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  2. H. Rennekamp
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  3. G. Luszpinski
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The paper includes parts of the thesis of G. Luszpinski

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Abshagen, U., Rennekamp, H. & Luszpinski, G. Pharmacokinetics of spironolactone in man. Naunyn-Schmiedeberg's Arch. Pharmacol. 296, 37–45 (1976). https://doi.org/10.1007/BF00498838

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  • DOI: https://doi.org/10.1007/BF00498838

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