Metyrapone - How It Works
Clinical pharmacology details from the US FDA-approved label: how Metyrapone works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex. Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary. With continued blockade of the enzymatic steps leading to production of cortisol and corticosterone, there is a marked increase in adrenocortical secretion of their immediate precursors, 11-desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and a corresponding elevation of these steroids in the plasma and of their metabolites in the urine. These metabolites are readily determined by measuring urinary 17‑hydroxycorticosteroids (17-OHCS) or 17-ketogenic steroids (17-KGS). Because of these actions, Metopirone is used as a diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsivene
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex.
Removal of the strong inhibitory feedback mechanism exerted by cortisol results in an increase in adrenocorticotropic hormone (ACTH) production by the pituitary.
With continued blockade of the enzymatic steps leading to production of cortisol and corticosterone, there is a marked increase in adrenocortical secretion of their immediate precursors, 11-desoxycortisol and desoxycorticosterone, which are weak suppressors of ACTH release, and a corresponding elevation of these steroids in the plasma and of their metabolites in the urine.
These metabolites are readily determined by measuring urinary 17‑hydroxycorticosteroids (17-OHCS) or 17-ketogenic steroids (17-KGS).
Because of these actions, Metopirone is used as a diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsiveness.
Metopirone may also suppress biosynthesis of aldosterone, resulting in a mild natriuresis.
12.2 Pharmacodynamics Metopirone exposure-response relationships and the time course of pharmacodynamic response are unknown.
12.3 Pharmacokinetics The mean C max of metyrapone following a single 750 mg is 3.7 mcg/mL falling to 0.5 mcg/mL 4 hours after administration.
Absorption The time to peak plasma concentration of metyrapone is approximately 1 hour after oral administration.
Elimination The mean (± SD) terminal elimination half‑lives of metyrapone and its active metabolite metyrapol are 1.9 (± 0.7) hours and approximately 4 hours, respectively.
Metabolism Metyrapone is reduced to metyrapol, an active alcohol metabolite.
Both metyrapone and metyrapol are conjugated with glucuronide.
Eight hours after a single oral dose, the ratio of metyrapone to its active metabolite metyrapol in plasma is 1:1.5.
Excretion Following administration of metyrapone 750 mg every 4 hours, approximately 5.3% of the dose was excreted in urine as unchanged and 38.5% as its active metabolite metyrapol within 72 hours after the first dose.
Pharmacokinetics
12.3 Pharmacokinetics The mean C max of metyrapone following a single 750 mg is 3.7 mcg/mL falling to 0.5 mcg/mL 4 hours after administration. Absorption The time to peak plasma concentration of metyrapone is approximately 1 hour after oral administration. Elimination The mean (± SD) terminal elimination half‑lives of metyrapone and its active metabolite metyrapol are 1.9 (± 0.7) hours and approximately 4 hours, respectively. Metabolism Metyrapone is reduced to metyrapol, an active alcohol metabolite. Both metyrapone and metyrapol are conjugated with glucuronide. Eight hours after a single oral dose, the ratio of metyrapone to its active metabolite metyrapol in plasma is 1:1.5. Excretion Following administration of metyrapone 750 mg every 4 hours, approximately 5.3% of the dose was excreted in urine as unchanged and 38.5% as its active metabolite metyrapol within 72 hours after the first dose.