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Biomedical subjects

M Doherty

Publications and source records attributed to M Doherty.

257 records · Page 15Linked to original sources
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Accessing the scientific literature. The reality of virtual scholarship.

The age-honored practice of plowing through the Index Medicus in a good medical library to meander through citations for treasured finds is an anachronism. Today, clinicians have the astonishing capacity to bring to bear existing knowledge almost effortlessly. Virtual scholarship makes available up-to-date medical citations and their abstracts. There can be access around the clock on any topic in the office, at the bedside, or from home. Computerized searches of the medical literature promote directed continuing education and may enhance clinical care of patients.

Databases, Bibliographic↗
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Species differences in the metabolism and disposition of spironolactone.

The absorption, excretion and metabolism of [22-14C]spironolactone was compared in Charles River rats, beagle dogs and rhesus monkeys. The drug was administered at the fixed dose of 5 mg/kg po and iv. From the po/iv ratios of the areas under the plasma radioactivity-time curves, the gastrointestinal absorption of the drug was estimated to be 82% in the rat, 62% in the dog, and 103% in the monkey. The absolute bioavailability of a pharmacologically active metabolite, canrenone, was 57% in the dog and 48% in the monkey. Spironolactone was extensively metabolized in all three species and differences existed in the composition of the metabolites in their plasma, urine, and feces. The amount of radioactivity that was excreted in the urine and feces of all three species was similar after either po or iv administration of the drug. The cumulative average excretion of radioactivity in the urine as percentage of the po dose in 6 days was 4.69% in the rat (N = 5), 18.5% in the dog (N = 3), and 46.0% in the monkey (N = 3). In the feces, the corresponding excretion values were 74.2, 69.3 and 40.1%, respectively. Canrenone excretion in the urine constituted 0.65% of the po dose in the rat, 0.82% in the dog, and 5.86% in the monkey, whereas the excretion of total fluorogenic metabolites constituted 1.1, 1.9, and 12.1% respectively. Comparison of animal data with those published for humans indicated that the disposition and metabolism of spironolactone in the rhesus monkey, rather than those in the rat or the dog, was closest to that in man.

Animals↗
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Spironolactone metabolism in man studied by gas chromatography-mass spectrometry.

Gas chromatography-mass spectrometry was used to identify metabolites of spironolactone in human blood and urine. In three healthy men about 20% of the radioactivity was excreted in the urine within 24 hr after an oral dose of [20-3H]spironolactone (200 mg + 200 muCi). About half of this radioactivity was extracted with chloroform at pH 3 and from this extract four stable metabolites were isolated by use of column and thin-layer chromatography. Two of these were the previously identified metabolites, canrenone (VII; 2.9% of dose) and the 6beta-hydroxy-sulfoxide (X; 1.8% of the dose). The remaining were the new metabolites, 15alpha-hydroxycanrenone (XI; 0.8% of dose) and the 6beta-hydroxy-thiomethyl derivatives (VI; 0.5% of dose). The principal water-soluble urinary metabolite was canrenoate ester glucuronide (XII; 4.5% of dose). In the 24- to 32-hr pooled serum, canrenone (VII) was the principal metabolite in the organic-extractable fraction; VI was present in appreciable amounts but X and XI were present at extremely low levels.

Canrenone↗