Aminoglutethimide
Aminoglutethimide Uses, Dosage, Side Effects, Food Interaction and all others data.
An aromatase inhibitor that produces a state of "medical" adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p454)
Aminoglutethimide inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.
| Trade Name | Aminoglutethimide |
| Availability | Discontinued |
| Generic | Aminoglutethimide |
| Aminoglutethimide Other Names | Aminoglutethimid, Aminoglutéthimide, Aminoglutethimide, Aminoglutethimidum, Aminoglutetimida, Aminoglutetimide, DL-Aminoglutethimide, p-Aminoglutethimide |
| Related Drugs | dexamethasone, estradiol, Premarin, Decadron, cyproheptadine, Arimidex, Xtandi, Ibrance, Femara, Xeloda |
| Type | Oral |
| Formula | C13H16N2O2 |
| Weight | Average: 232.2783 Monoisotopic: 232.121177766 |
| Protein binding | 21-25% |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Aminoglutethimide is an adrenocortical steroid synthesis inhibitor used in the treatment of Cushing's syndrome.
For the suppression of adrenal function in selected patients with Cushing's syndrome, malignant neoplasm of the female breast, and carcinoma in situ of the breast.
How Aminoglutethimide works
Aminoglutethimide reduces the production of D5-pregnenolone and blocks several other steps in steroid synthesis, including the C-11, C-18, and C-21 hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P-450 complexes. Specifically, the drug binds to and inhibits aromatase which is essential for the generation of estrogens from androstenedione and testosterone. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion.
Toxicity
Oral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100. Symptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomiting.
Food Interaction
- Take with or without food. The absorption is unaffected by food.
Aminoglutethimide Drug Interaction
Major: fentanyl, fentanylModerate: zolpidem, zolpidemUnknown: acetaminophen, acetaminophen, aspirin, aspirin, rabeprazole, rabeprazole, amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, oxymetazoline nasal, oxymetazoline nasal, palonosetron, palonosetron, alprazolam, alprazolam, tryptophan, tryptophan
Aminoglutethimide Disease Interaction
Elimination Route
Rapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
Half Life
12.5 ± 1.6 hours
Elimination Route
After ingestion of a single oral dose, 34%-54% is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as the N-acetyl derivative.
Innovators Monograph
You find simplified version here Aminoglutethimide
