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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1977-3-21
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0028-1298
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
296
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37-45
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pubmed:dateRevised |
2010-3-12
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pubmed:meshHeading |
pubmed-meshheading:1012347-Administration, Oral,
pubmed-meshheading:1012347-Adult,
pubmed-meshheading:1012347-Aged,
pubmed-meshheading:1012347-Biotransformation,
pubmed-meshheading:1012347-Chromatography, Thin Layer,
pubmed-meshheading:1012347-Feces,
pubmed-meshheading:1012347-Fluorometry,
pubmed-meshheading:1012347-Humans,
pubmed-meshheading:1012347-Kinetics,
pubmed-meshheading:1012347-Male,
pubmed-meshheading:1012347-Spironolactone,
pubmed-meshheading:1012347-Time Factors
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pubmed:year |
1976
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pubmed:articleTitle |
Pharmacokinetics of spironolactone in man.
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pubmed:publicationType |
Journal Article
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