Document Detail

Influence of spironolactone pretreatment on pharmacokinetics and metabolism of digitoxin in rats.
MedLine Citation:
PMID:  1143356     Owner:  NLM     Status:  MEDLINE    
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.
H F VOHRINGER; L Weller; N Rietbrock
Related Documents :
2777046 - Effect of secretin on bile formation in rats with cirrhosis of the liver: structure-fun...
7292506 - Hepatobiliary transport and organ distribution of silver in the rat as influenced by se...
16896816 - Effects of dexamethasone on small bowel and kidney oxidative stress and histological al...
25067936 - Serum biochemical assessment of hepatic and renal functions of rats during oral exposur...
23827506 - Modeling the effects of low toxin levels in food on feeding: dose-dependent reduction o...
21724106 - Rosuvastatin, a new generation 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibito...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  287     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  1975  
Date Detail:
Created Date:  1975-10-10     Completed Date:  1975-10-10     Revised Date:  2010-03-12    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  129-39     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Chromatography, Thin Layer
Digitoxigenin / metabolism
Digitoxin / metabolism*
Digoxin / metabolism
Drug Interactions
Glucuronates / metabolism
Liver / metabolism
Spironolactone / pharmacology*
Reg. No./Substance:
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

Previous Document:  A micropuncture study of the effect of isoprenaline on renal tubular fluid and electrolyte transport...
Next Document:  Functional and fine structural characteristics of the sensory neuron blocking effect of capsaicin.