Non-interaction of spironolactone medication and cortisol metabolism in man

  title={Non-interaction of spironolactone medication and cortisol metabolism in man},
  author={Ulrich Abshagen and S. Sp{\"o}rl and M. L'age},
  journal={Klinische Wochenschrift},
ZusammenfassungBei 5 gesunden Probanden und bei 5 Patienten mit dekompensierten Lebererkrankungen wurden die Konzentrationen von Cortisol und von Canrenon und Canrenoat-K im Plasma nach jeweils einer Einzeldosis von 7 mg Spironolakton/kg mit und ohne 12tägiger Vorbehandlung mit Spironolakton über jeweils 4 Tage verfolgt. Die Bestimmung der Spironolaktonmetabolite erfolgte fluorimetrisch. Das Cortisol im Plasma wurde mit einem hochspezifischen Radioimmunoassay mit vorgeschalteter… Expand
Interference of spironolactone therapy with adrenal steroid metabolism in secondary hyperaldosteronism
Electrolytes in serum and urine, multiple serum steroids, plasma renin activity (PRA), angiotensin II (AT II) levels in plasma, aldosterone secretion rate, excretion of ald testosterone-18-glucuronide and drug concentrations in plasma were measured throughout the study. Expand
Elevated resting and exercise-induced cortisol levels after mineralocorticoid receptor blockade with canrenoate in healthy humans.
It is concluded that MR blockade leads to a tonically increased cortisol secretion both during rest and under stimulation, which suggests that blockade of MR shifts the set point for cortisol feedback inhibition of the HPA axis toward higher cortisol levels. Expand
Displacement of cortisol from human heart by acute administration of a mineralocorticoid receptor antagonist.
Human cardiac 11β-HSD2 activity appears too low to inactivate cortisol to cortisone and may contribute to adverse MR activation in human heart. Expand
Abiraterone and spironolactone in prostate cancer: a combination to avoid
Although spironolactone generally exerts anti-androgenic effects, experimental evidence exists that it acts as an androgens receptor agonist in an androgen-depleted environment, capable of inducing prostate cancer proliferation and should be avoided in prostate cancer patients suffering from treatment-associated side effects of abiraterone. Expand
Corticosteroids mediate fast feedback of the rat hypothalamic-pituitary-adrenal axis via the mineralocorticoid receptor.
It is suggested that mineralocorticoids can dynamically regulate basal corticosterone concentrations during the diurnal peak, a time of day when there is already a high level of occupancy of the cytoplasmic mineralOCorticoid receptor. Expand


Disposition kinetics of spironolactone in hepatic failure after single doses and prolonged treatment
Four out of 6 patients with histologically characterised, decompensated liver disease who had not previously received spironolactone showed marked acceleration in the rate of elimination of radioactivity from plasma and a corresponding increase in excretion of labelled compounds in urine. Expand
Influence of spironolactone on endogenous steroid metabolism in man.
Results are interpreted as being due to an initial inhibition of aldosterone synthesis by spironolactone, which is finally compensated, at least in part, by increased activation of the renin-angiotensin system. Expand
Effects of spironolactone, canrenone and canrenoate-K on cytochrome P450, and 11beta- and 18-hydroxylation in bovine and human adrenal cortical mitochondria.
Findings indicate that at low concentrations spironolactone and its major metabolites, canrenone and canrenoate-K, or their hydroxylated metabolites,can directly interfere with the biosynthesis of aldosterone in bovine and certain human adrenal cortical tissue. Expand
Pharmacokinetics of spironolactone in man
The observed increase in the speed of elimination of radioactivity from plasma, together with an observed increase of the polar fraction in urine from 35 up to 85%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. Expand
Mechanism of action of spironolactone on adrenocortical function in guinea pigs.
The results indicate that spironolactone administration diminishes the activity of adrenal mitochondrial as well as microsomal cytochrome P-450-containing enzymes, resulting in a fall in corticosteroid output. Expand
Interference in the measurement of plasma 11-hydroxycorticosteroids caused by spironolactone administration.
Administration of spironolactone was shown to be associated with a prompt, striking and sustained increase in plasma Mattingly fluorogens, indicating that the response was not due to an alteration in endogenous steroid metabolism. Expand
β-Methyl-Digoxin Disposition During Spironolactone Treatment
Some years ago (Abshagen, 1973) we showed that the pharmacokinetics of β-methyl-digoxin in female SD rats were markedly influenced by a 3-day pretreatment with 100 mg spironolactone/kg b.i.d. AfterExpand
Conversion of spironolactone to canrenone and disposition kinetics of spironolactone and canrenoate-potassium in rats
It can be concluded that hydrolysis of the 7 α-thioacetyl I to the 7α-thiol VI is a very rapid metabolic step, that the γ-lactone ring is in a rapid enzymatic equilibrium with the corresponding ε-hydroxylic acids, and that elimination of H2S from VI yielding II is the overall rate limiting step in the metabolic conversion of I to II. Expand
Spironolactone and plasma cortisol
The fluorimetric method of Mattingly was used to determine how rapidly the spurious elevation of plasma cortisol develops after spironolactone administration and to define the rate of disappearance of the artifact from plasma. Expand
Increased plasma 11-deoxycorticosterone during spironolactone medication.
The increase of plasma deoxycorticosterone (DOC) levels after administration of spironolactone is a real effect and not due to cross-interference of the drug or its metabolites with the DOC-assay.Expand