| Influence of spironolactone pretreatment on pharmacokinetics and metabolism of digitoxin in rats. | |
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MedLine Citation:
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PMID: 1143356 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The influence of pretreatment with spironolactone (84 mg/kg at 3 days, twice per day) on the tritium levels in plasma, urine and feces of female SD-rats (n=9) was investigated at various time periods after oral administration of 25mug/kg -3H-digitoxin. In plasma, the concentrations of total radioactivity are reduced in pretreated animals to about 20% of tritium levels in control rats, while the half-life of radioactivity in both groups is almost identical, 2.9 days in pretreated rats and 2.8 days in controls. The lower plasma levels of tritium in pretreated rats coincide with a six-fold decrease in the urinary -3H-elimination and a corresponding increase in the fecal excretion. This is due to a higher biliary clearance of tritiated products in the early phase of elimination. The separation of the excretion products by TLC shows that spironolactone pretreatment enhances the splitting of the glycosidic bonds of digitoxin. The amount of digitoxigenin-bis-digitoxoside and of digitoxigenin-mono-digitoxoside excreted in urine and feces within 96 hrs is four and ten times greater than that recovered in control animals, respectively. The formation of the hydroxylation products digoxin and digoxigenin-bis-digitoxoside is decreased from 50% of the total excreted radioactivity in control to 15% in pretreated rats. The conjugation reactions with glucuronic and sulfuric acid are increased after pretreatment with spironolactone. Thus, the effect of spironolactone on digitoxin kinetics is apparently related to an enhancement of the hepatic excretory mechanism as well as to an enhanced metabolism. |
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Authors:
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H F VOHRINGER; L Weller; N Rietbrock |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Naunyn-Schmiedeberg's archives of pharmacology Volume: 287 ISSN: 0028-1298 ISO Abbreviation: Naunyn Schmiedebergs Arch. Pharmacol. Publication Date: 1975 |
Date Detail:
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Created Date: 1975-10-10 Completed Date: 1975-10-10 Revised Date: 2010-03-12 |
Medline Journal Info:
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Nlm Unique ID: 0326264 Medline TA: Naunyn Schmiedebergs Arch Pharmacol Country: GERMANY, WEST |
Other Details:
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Languages: eng Pagination: 129-39 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chloroform Chromatography, Thin Layer Digitoxigenin / metabolism Digitoxin / metabolism* Digoxin / metabolism Drug Interactions Female Glucuronates / metabolism Half-Life Hydroxylation Kinetics Liver / metabolism Rats Solubility Spironolactone / pharmacology* Tritium |
| Chemical | |
Reg. No./Substance:
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0/Glucuronates; 10028-17-8/Tritium; 143-62-4/Digitoxigenin; 20830-75-5/Digoxin; 52-01-7/Spironolactone; 67-66-3/Chloroform; 71-63-6/Digitoxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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