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  • Title: Increased metabolism to dihydrodigoxin after intake of a microencapsulated formulation of digoxin.
    Author: Magnusson JO, Bergdahl B, Bogentoft C, Gustafsson S, Jonsson UE.
    Journal: Eur J Clin Pharmacol; 1984; 27(2):197-202. PubMed ID: 6499898.
    Abstract:
    A capsule preparation containing small, enteric-coated granules of digoxin was developed to prevent acid hydrolysis of the drug in the stomach and to diminish the variation in plasma glycoside concentration during the intervals between doses. The absorption and metabolism of tritiated digoxin after a single oral loading dose of this formulation (Formulation C) were compared to those after ingestion of a digoxin solution (Formulation S) by 8 healthy men. Drug concentrations were measured by radioimmunoassay (RIA) and liquid chromatography (LC). The percentage of the digoxin dose excreted in the urine during 72 h, as measured by RIA, was significantly lower after the capsule (20.5 +/- 2.0% vs 36.2 +/- 3.0% after S, mean +/- SEM) but total urinary radioactivity after the two treatments was similar (C 35.3 +/- 5.2 and S 41.2 +/- 2.6%; p greater than 0.05). The discrepancy was mainly due to significantly greater excretion of dihydrodigoxin after the capsule (m 12.8%, range 0-28.6% of the dose) than after the digoxin solution (m 5.4%, range 0-14.5%). Dihydrodigoxin was not measured by the RIA. The recovery of hydrolysis metabolites (LC) was greater during the first 24 h after S (2.3 +/- 0.6% vs 0.9 +/- 0.3% after C; p less than 0.05). The peak plasma concentration of digoxin (RIA) was significantly reduced and delayed after intake of C (2.5 +/- 0.4 nmol/l at 3.8 +/- 0.3 h vs. 8.3 +/- 0.8 nmol/l at 0.9 +/- 0.1 h after S), and so was the shortening of electromechanical systole at 1.5 h, 2.5 h, and 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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