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Cytadren (aminoglutethimide) inhibits the enzymatic conversion of cholesterol to Δ⁵-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens.

Cytadren (aminoglutethimide) 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 Cytadren (aminoglutethimide) to cytochrome P-450 complexes.

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 Cytadren (aminoglutethimide) . The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since Cytadren (aminoglutethimide) increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement.

Although Cytadren (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 Cytadren (aminoglutethimide) . In spite of an increase in TSH, Cytadren (aminoglutethimide) has not been associated with increased prolactin secretion.

Note: Cytadren (aminoglutethimide) was marketed previously as an anticonvulsant but was withdrawn from marketing for that indication in 1966 because of the effects on the adrenal gland.

Pharmacokinetics

Cytadren (aminoglutethimide) is rapidly and completely absorbed after oral administration. In 6 healthy male volunteers, maximum plasma levels of Cytadren (aminoglutethimide) averaged 5.9 µg/mL at a median of 1.5 hours after ingestion of two 250-mg tablets. The bioavailability of tablets is equivalent to equal doses given as a solution. 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.

The half-life of Cytadren (aminoglutethimide) in normal volunteers given single oral doses averaged 12.5 ± 1.6 hours.

Upon withdrawal of therapy with Cytadren (aminoglutethimide) , the ability of the adrenal glands to synthesize steroid returns, usually within 72 hours.

Clinical Studies In Children

Clinical investigations included 9 patients aged 2 1/2 to 16 years; 4 of these were aged 10 or less. Seven of the patients received other therapies (drugs or irradiation) either with Cytadren (aminoglutethimide) or within a short period before initiation of therapy with Cytadren (aminoglutethimide) . Diagnoses included 5 patients with adrenal carcinoma, 3 with adrenal hyperplasia, and 1 with ectopic ACTH-producing tumor. Duration of treatment ranged from 3 days to 6 1/2 months. Dosages ranged from 0.375 g to 1.5 g daily. In general, smaller doses were used for younger patients; for example, a 2 1/2-year- old received 0.5-0.75 g daily, a 3 1/2-year-old received 0.5 g daily, and all others over 10 years of age received 0.75-1.5 g daily. Results are difficult to evaluate because of the concomitant therapy, duration of therapy, or inadequate laboratory documentation. Most patients did show decreases in plasma or urinary steroids at some time during treatment, but these may have been due to other therapeutic modalities or their combinations.

Last reviewed on RxList: 1/15/2009
This monograph has been modified to include the generic and brand name in many instances.