| Stereochemistry | ABSOLUTE |
| Molecular Formula | C14H14N2O.2C4H6O6 |
| Molecular Weight | 526.4474 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O[C@H]([C@@H](O)C(O)=O)C(O)=O.O[C@H]([C@@H](O)C(O)=O)C(O)=O.CC(C)(C(=O)C1=CN=CC=C1)C2=CC=CN=C2
InChI
InChIKey=FBSAWAHQGRDEJD-WBPXWQEISA-N
InChI=1S/C14H14N2O.2C4H6O6/c1-14(2,12-6-4-8-16-10-12)13(17)11-5-3-7-15-9-11;2*5-1(3(7)8)2(6)4(9)10/h3-10H,1-2H3;2*1-2,5-6H,(H,7,8)(H,9,10)/t;2*1-,2-/m.11/s1
Metyrapone (trade name Metopirone) is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome (hypercortisolism). Metopirone, metyrapone USP, is an inhibitor of endogenous adrenal corticosteroid synthesis, available
as 250-mg capsules for oral administration. The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by
inhibiting the 11-β-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.
CNS Activity
Originator
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Sourcing
PubMed
Patents
Sample Use Guides
Single-Dose Short Test
This test, usually given on an outpatient basis, determines plasma 11-desoxycortisol and/or ACTH
levels after a single dose of Metopirone (Metyrapone). The patient is given 30 mg/kg (maximum 3 g Metopirone) at
midnight with yogurt or milk. The same dose is recommended in children. The blood sample for the
assay is taken early the following morning (7:30-8:00 a.m.). The plasma should be frozen as soon as
possible. The patient is then given a prophylactic dose of 50 mg cortisone acetate.
Multiple-Dose Test
Day 1: Control period - Collect 24-hour urine for measurement of 17-OHCS or 17-KGS.
Day 2: ACTH test to determine the ability of adrenals to respond - Standard ACTH test such as
infusion of 50 units ACTH over 8 hours and measurement of 24-hour urinary steroids. If results
indicate adequate response, the Metopirone test may proceed.
Day 3-4: Rest period.
Day 5: Administration of Metopirone: Recommended with milk or snack.
Adults: 750 mg orally, every 4 hours for 6 doses. A single dose is approximately equivalent to 15
mg/kg.
Children: 15 mg/kg orally every 4 hours for 6 doses. A minimal single dose of 250 mg is
recommended.
Day 6: After administration of Metopirone - Determination of 24-hour urinary steroids for effect.
Route of Administration:
Oral
ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD
