Metyrapone

Pharmacodynamics

The pharmacological effect of Metopirone (metyrapone) 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 (metyrapone) is used as a diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsiveness. Metopirone (metyrapone) may also suppress biosynthesis of aldosterone, resulting in a mild natriuresis.

Pharmacokinetics

The response to Metopirone (metyrapone) does not occur immediately. Following oral administration, peak steroid excretion occurs during the subsequent 24-hour period.

Metopirone (metyrapone) is absorbed rapidly and well when administered orally as prescribed. Peak plasma concentrations are usually reached 1 hour after administration. After administration of 750 mg, mean peak plasma concentrations are 3.7 µg/mL, falling to 0.5 µg/mL 4 hours after administration. Following a single 2000-mg dose, mean peak plasma concentrations of metyrapone in plasma are 7.3 µg/mL.

The major biotransformation is reduction of the ketone to metyrapol, an active alcohol metabolite. Eight hours after a single oral dose, the ratio of metyrapone to metyrapol in the plasma is 1:1.5. Metyrapone and metyrapol are both conjugated with glucuronide.

Metyrapone is rapidly eliminated from the plasma. The mean ± SD terminal elimination half-life is 1.9 ± 0.7 hours. Metyrapol takes about twice as long as metyrapone to be eliminated from the plasma. 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.

Metyrapone is used in the diagnosis of certain problems of the adrenal glands. These glands are located near the kidneys. The adrenal glands produce a steroid chemical called cortisol (hydrocortisone) that helps the body respond to stress or illness. From the results of a metyrapone test, your doctor will be able to tell if your adrenal glands produce the correct amount of cortisol under stress or during illnesses.

How test is done: Metyrapone is taken by mouth in one or more doses the day before the testing is done. The next day, blood and/or urine samples are taken. A tube called a catheter may be placed in your bladder to help take the urine sample. The amount of hormones in your blood or urine is measured. Then the results of the test are studied.

Metyrapone may also be used for other conditions as determined by your doctor.

Metyrapone is available only with your doctor's prescription.

metyrapone may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to metyrapone before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert .

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with yogurt or milk as your doctor has told you.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about metyrapone, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about metyrapone. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using metyrapone.

Review Date: October 4, 2017