Metyrapone

226.27

226.27

200-206-2

ZS9KD92H6V

760076|25265

DTXSID1023314

C47619

CRYSTALS FROM ETHER & PENTANE|WHITE TO LIGHT AMBER, FINE CRYSTALLINE POWDER

V - Various

2933399090

42.8

2

Solid

1.1±0.1 g/cm3

50-51 °C

384.4°C at 760 mmHg

>230 °F

1.565

Sparingly soluble with water.

Store at +4°C

CHARACTERISTIC ODOR

FORMS WATER-SOLUBLE SALTS WITH ACIDS

NONH for all modes of transport

3

22-36/37/38

26

UC3050000

Xn

PROTECT TABLETS FROM EXCESSIVE HEAT & LIGHT TO PREVENT DISCOLORATION & DEGRADATION.

P301 + P312 + P330-P305 + P351 + P338

H302-H315-H319-H335

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 41 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Oral LD50 in rats is 521 mg/kg. One case has been recorded in which a 6-year-old girl died after two doses of Metopirone, 2 g. Symptoms of overdose include cardiac arrhythmias, hypotension, dehydration, anxiety, confusion, weakness, impairment of consciousness, nausea, vomiting, epigastric pain, and diarrhea.

SUBNORMAL RESPONSE TO METYRAPONE MAY...OCCUR IN PT RECEIVING ESTROGENS, PROGESTOGENS, CORTICOSTEROIDS, PHENOTHIAZINES, CHLORDIAZEPOXIDE, CHLORPROMAZINE, AMITRIPTYLINE, PHENOBARBITAL, OR METHYSERGIDE. ESTROGEN-PROGESTOGEN ORAL CONTRACEPTIVES...REPORTED TO BOTH REDUCE & ELEVATE RESPONSE TO METYRAPONE.|PRETREATMENT WITH METYRAPONE PROVOKED HYPERSECRETION OF FSH FOLLOWING SINGLE INJECTION OF LRH.|METYRAPONE REDUCED METABOLITE FORMATION BY 3-HYDROXYLATION & N-1-DEMETHYLATION, BUT HAD NO EFFECT ON C-4'-HYDROXYLATION OF DIAZEPAM.|POTENTIATION OF HYPOTHALAMIC-PITUITARY-ADRENAL RESPONSE TO METYRAPONE BY L-DOPA IN ACROMEGALIC PATIENT.

Used as a diagnostic drug for testing hypothalamic-pituitary ACTH function. Occasionally used in Cushing's syndrome.

METYRAPONE IS USED TO TEST ABILITY OF PITUITARY TO RESPOND TO DECR CONCN OF PLASMA CORTISOL. ADMIN...TO PT WITH DISEASE OF HYPOTHALAMICO-PITUITARY COMPLEX.../IS/ NOT FOLLOWED BY INCR RENAL EXCRETION OF "17-HYDROXYCORTICOIDS."|.../METYRAPONE HAS/ BEEN USED WITH SPIRONOLACTONE & PREDNISONE TO RELIEVE SEVERE EDEMA, BUT...HAS BEEN REPLACED BY MORE POTENT DIURETICS. .../ALSO/ USED INVESTIGATIONALLY TO LOWER PLASMA CHOLESTEROL LEVELS IN PT WITH FAMILIAL HYPERCHOLESTEROLEMIA TYPE II, BUT WELL-CONTROLLED CLINICAL STUDIES...NOT YET AVAILABLE.|METYRAPONE MAY BE USED TO CONFIRM DEXAMETHASONE SUPPRESSION TEST RESULTS IN DIFFERENTIAL DIAGNOSIS OF ADRENAL HYPERPLASIA & ADRENAL ADENOMA...RESULTS OF THIS TEST MUST BE INTERPRETED CAUTIOUSLY.|METYRAPONE HAS BEEN USED EXPTL TO TREAT HYPERCORTISOLISM THAT RESULTS FROM ADRENAL NEOPLASMS THAT FUNCTION AUTONOMOUSLY & FROM ECTOPIC ACTH PRODUCTION BY TUMORS. IT IS NOT SUITABLE FOR CORRECTING EXCESSIVE CORTISOL SECRETION OF CUSHING'S SYNDROME CAUSED BY HYPERSECRETION OF PITUITARY ACTH.|...ADMIN OF METYRAPONE CAN BE USED AS TEST FOR NORMAL HYPOTHALAMICO-PITUITARY FUNCTION ONLY IF ADRENAL GLANDS ARE CAPABLE OF RESPONDING TO ACTH...

IN HIGH DOSES, METYRAPONE MAY INHIBIT 18- & 19-HYDROXYLASE ENZYMES, THUS INHIBITING SYNTHESIS OF OTHER STEROIDS, INCL ESTROGENS. ...DRUG MAY ALSO DECR PLASMA HALF-LIFE OF CORTISOL, INCR GROWTH HORMONE RELEASE, & INDUCE HYPERGLYCEMIA.|...DRUG MAY INDUCE ACUTE ADRENAL INSUFFICIENCY IN PT WITH REDUCED ADRENAL SECRETORY CAPACITY. METYRAPONE ALSO INHIBITS SYNTHESIS OF ALDOSTERONE... HOWEVER.../IT/ DOES NOT TYPICALLY CAUSE DEFICIENCY IN MINERALOCORTICOIDS, WITH CONSEQUENT LOSS OF SODIUM & RETENTION OF POTASSIUM...|OCCASIONALLY, ARTERIAL BLOOD PRESSURE MAY FALL & MODERATE INCR IN PULSE RATE MAY INSUE. ...SHOULD NOT BE USED IN PT WITH ADRENOCORTICAL INSUFFICIENCY...SAFE USE OF DRUG IN PREGNANCY HAS NOT BEEN ESTABLISHED.|ABILITY OF ADRENAL TO RESPOND TO ACTH SHOULD BE DEMONSTRATED BEFORE METYRAPONE IS EMPLOYED...|For more Drug Warnings (Complete) data for METYRAPONE (8 total), please visit the HSDB record page.

Metopirone is an inhibitor of endogenous adrenal corticosteroid synthesis.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)|Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033) (See all compounds classified as Antimetabolites.)

Absorbed rapidly and well when administered orally. Peak plasma concentrations are usually reached 1 hour after administration.|After administration of 4.5 g metyrapone (750 mg every 4 hours), an average of 5.3% of the dose was excreted in the urine in the form of metyrapone (9.2% free and 90.8% as glucuronide) and 38.5% in the form of metyrapol (8.1% free and 91.9% as glucuronide) within 72 hours after the first dose was given.|GASTROINTESTINAL ABSORPTION OF METYRAPONE IS VARIABLE. FOLLOWING ORAL ADMIN OF 750 MG OF METYRAPONE EVERY 4 HR TO NORMAL PT, PEAK PLASMA LEVELS OF ABOUT 1.2 UG M/L...REACHED AFTER THIRD DOSE...0.4 UG/ML...PRESENT IMMEDIATELY AFTER SIXTH DOSE.|...PLASMA LEVELS OF METYRAPONE...IN RATS WERE SHOWN TO EXHIBIT A CIRCADIAN PATTERN WHEN ANIMALS WERE KEPT IN ALTERNATING 12-HR LIGHT-12 HR DARK REGIMEN. HALF-LIFE...OBSERVED @ 10:00 PM WAS APPROX 2.5 TIMES LONGER THAN THAT OBSERVED @ 10:00 AM...|...WITHIN 2 DAYS FOLLOWING ORAL ADMIN OF 750 MG...EVERY 4 HR FOR 6 DOSES, APPROX 0.5%...IS EXCRETED IN URINE UNCHANGED, 3% IS EXCRETED AS REDUCED METABOLITE, & 37% AS GLUCURONIDE CONJUGATES OF METYRAPONE & ITS METABOLITES.

Hepatic. The major biotransformation is reduction of the ketone to metyrapol, an active alcohol metabolite. Metyrapone and metyrapol are both conjugated with glucuronide.|/METYRAPONE IS METABOLIZED BY/ ONE ENZYME, PRESENT IN MICROSOMAL FRACTION OF RAT LIVER, IS NADPH-DEPENDENT & IS ACTIVE UNDER AEROBIC CONDITIONS, REDUCING COMPD TO 2-METHYL-1,2-BIS-(3-PYRIDYL)PROPAN-1-OL...SECOND ENZYME...HAS NOT BEEN IDENTIFIED...

1.9 ±0.7 hours.|METYRAPONE HAS PLASMA HALF-LIFE OF ABOUT 20-26 MIN.

The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-ß-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.|METYRAPONE REDUCES CORTISOL PRODUCTION BY INHIBITION OF 11BETA-HYDROXYLATION REACTION. BIOSYNTHETIC PROCESS IS TERMINATED @ 11DESOXYCORTISOL... IN NORMAL PERSON...INCR IN ACTH RELEASE FOLLOWS, & SECRETION OF 11DESOXYCORTISOL...ACCELERATED.|ORAL ADMIN OF 250 MG/SQ M BODY SURFACE INCR PLASMA CONCN OF GLUCOSE & GROWTH HORMONE IN CHILDREN.|@ LOW DOSES PGE2 & PGF2ALPHA RELEASE WERE STIMULATED. @ HIGHER DOSES PGF2ALPHA RELEASE WAS INHIBITED.

DISCONTINUE DRUG & ADMIN CORTISONE /PRC: OR CORTISOL OR RELATED GLUCOCORTICOID/.

UNTOWARD EFFECTS INCL THROMBOPHLEBITIS. LESS SERIOUS EFFECTS INCL ANOREXIA, NAUSEA, ABDOMINAL DISCOMFORT, DIARRHEA, DIZZINESS, VERTIGO, HEADACHE, & SEDATION.|METYRAPONE MAY POTENTIALLY PRODUCE ACUTE ADRENAL INSUFFICIENCY & EVEN DEATH IN PT WITH REDUCED ADRENAL SECRETORY CAPACITY...|METYRAPONE HAS A LOW ORDER OF TOXICITY.

Métopirone

METYRAPONE, USP. ...IS MARKETED AS 250-MG ORAL TABLETS & AS SOLN OF DITARTRATE SALT (100 MG/ML EQUIV TO 43.8 MG/ML OF BASE) IN 10-ML AMPULS FOR IV ADMIN.

USE OF METYRAPONE & APPLICATION OF MUTUAL DEPLETION SYSTEM KINETICS HAS LED TO MEASUREMENT OF CONCN OF CATALYTICALLY ACTIVE & METYRAPONE-SENSITIVE CENTERS OF CYTOCHROME P450 & THEIR TURNOVER NUMBERS...

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients