Fairly rapidly absorbed from the gastrointestinal tract
Food increases the bioavailability of unmetabolized spironolactone by almost 100%.
Spironolactone and its metabolites are more than 90% bound to plasma proteins.
Spironolactone is a synthetic 17-lactone steroid
Renal competitive aldosterone antagonist
On its own, spironolactone is only a weak diuretic
It may be given alone or with other diuretic agents which act more proximally in the renal tubule
Due to its anti-androgen effect, it can also be used to treat hirsutism
Common component in hormone therapy for male-to-female transgendered people
Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptor in the distal tubule cells
Antagonises a cytoplasmic mineralocorticoid receptor responsible for enhancing expression of Na+, K+-ATPase and the Na+ channel involved in a Na+ K+ transport in the distal tubule
This increases the secretion of water and sodium, while decreasing the excretion of potassium
Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly.
Half-life 10 mins
Rapidly and extensively metabolized
Divided into two main routes
those in which the sulfur moiety is retained
those in which the sulfur moiety is removed by dethioacetylation.
Transformed to a reactive metabolite
Can inactivate adrenal and testicular cytochrome P450 enzymes
Has anti-androgenic activity.
Excreted primarily in the urine and secondarily in bile
Oral LD50 of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits
Acute overdosage of spironolactone may be manifested by:
Drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea
Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats.