THE METABOLISM AND BIOPHARMACEUTICS OF SPIRONOLACTONE IN MAN

@article{Overdiek1987THEMA,
  title={THE METABOLISM AND BIOPHARMACEUTICS OF SPIRONOLACTONE IN MAN},
  author={H W Overdiek and Frans W. H. M. Merkus},
  journal={Drug Metabolism and Drug Interactions},
  year={1987},
  volume={5},
  pages={273 - 302}
}
Spironolactone, a competitive aldosterone antagonist, has been used for almost 30 years in those disorders associated with primary or secondary hyperaldosteronism. This review is confined to its metabolism and biopharmaceutics in man. Spironolactone undergoes extensive metabolism with no unchanged drug appearing in the urine. Its metabolites can be divided into two main categories: those in which the sulfur of the parent molecule is removed and those in which the sulfur is retained. The… Expand
Simultaneous determination of spironolactone and its metabolites in human plasma.
TLDR
The precision and accuracy of the method were confirmed by relative standard deviations below 10% for different concentrations, except for the concentration equal to the quantitation limit, where these parameters ranged from 12-15%. Expand
Improved bioavailability from a spironolactone beta-cyclodextrin complex
TLDR
Pharmacokinetic analysis revealed that the mean relative bioavailability of the spironolactone beta cyclodextrin complex and micronised powder when compared with spironlactone tablets (Aldactone) was 252% and 124%, respectively, which was no change in the canrenone elimination half lives of each subject. Expand
[Inhibitory effect of carbamazepine on hypotensive action of spironolactone in primary aldosteronism].
TLDR
This case shows for the first time the existence of a drug interaction between spironolactone and any anti-epileptic drug in primary aldosteronism, and replacement of carbamazepine with gabapentin prevented these drug-induced increases in blood pressure in the patient. Expand
YEARS OF THE MINERALOCORTICOID RECEPTOR Mineralocorticoid receptor antagonists : 60 years of research and development
The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which wasExpand
Microbial synthesis of mammalian metabolites of spironolactone by thermophilic fungus Thermomyces lanuginosus
Graphical abstract Figure. No caption available. HighlightsA thermophilic fungus generated four major mammalian metabolites of spironolactone.Metabolic pattern of Thermomyces lanuginosus is similarExpand
30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development
TLDR
Novel non-steroidal MRAs such as apararenone, esaxerenone and finerenone are in late-stage clinical trials in patients with heart failure, chronic kidney disease, hypertension and liver disease and the history of the various generations of MRAs is reflected. Expand
The evolution of aldosterone antagonists
TLDR
Eplerenone represents a molecule with improved steroid receptor selectivity and pharmacokinetic properties in man compared to spironolactone, and it is demonstrated that these improvements translate into tolerability and efficacy in patients with cardiovascular disease. Expand
Evaluation of Spironolactone Bioavailability from Solutions of ß-Cyclodextrin Derivatives in Rats
TLDR
Water-soluble derivatives of s-cyclodextrin have been considered for the solubilization of SP in order to formulate a safe liquid preparation, which would also provide more concistent delivery of SP. Expand
Aldosterone-receptor antagonism and end-stage renal disease
TLDR
Pilot safety studies with aldosterone-receptor antagonists in ESRD patients have begun, implying that spironolactone can be safely used in carefully selected and closely monitored patients. Expand
Aldosterone receptor antagonists: Biology and novel therapeutical applications
TLDR
The addition of aldosterone antagonists to the conventional therapy of myocardial failure and of selected cases of hypertension thus appears beneficial, resulting in an improved survival rate and a reduced incidence of cardiac complications. Expand
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The results of the two studies seem inconsistent with the view that canrenone alone is responsible for the pharmacological activity of both drugs, and suggest that a significant part of the activity of spironolactone may be attributable to metabolites other than canren one. Expand
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TLDR
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TLDR
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