Aminoglutethimide dosing

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

The contraceptive efficacy of depot medroxyprogesterone acetate does not appear to be affected by interactions with other drugs some interactions are known (6), but the doses used for contraceptive purposes are sufficient to remain effective even if metabolism is increased, for example by aminoglutethimide or phenytoin. 

Disposition in the Body. Readily absorbed after oral administration. About 10% of an oral dose is excreted in the urine as unchanged drug in 48 hours acetamidoglutethimide has been identified as a metabolite. Aminoglutethimide appears to induce its own metabolism. 

Precautions Aminoglutethimide administered with adrenal replacement doses of hydrocortisone. Hypercalcemia may occur in patients with bone metastases. Use in combination with IHRH agonist. ... 

Aminoglutethimide (Cytadren AG), a first-generation type 2 AI, originally was developed as an anticonvulsant but was subsequently found to inhibit the synthesis of adrenocortical steroids. AG is a nonspecific weak AI, administered as a 250-mg dose four times daily with hydrocortisone supplementation because of unwanted adrenal suppression. Because of significant toxicides related to its anticonvulsant structure and its relatively weak inhibition of aromatase, its use has declined considerably with the advent of newer AIs. 

In a study in 9 patients being treated for breast cancer, a low-dose aminoglutethimide regimen (125 mg twiee daily) increased the elearanee of a single-dose ofR- or 5-warfarin by 41.2% with marked variability between individuals (range 15 to 103%). A high-dose regimen (250 mg four times daily) inereased the clearance by 90.8%. The effeets of the interae-tion had developed fully by 14 days. Both enantiomers of warfarin were equally affeeted. ... 

Both interactions appear to be established and are possibly clinically important. A 50% reduction in the plasma levels of medroxyprogesterone and megestrol should be expected during concurrent use, and this may reduce the adrenal suppressive effect. The authors of one report say that to achieve adequate plasma medroxyprogesterone acetate levels in breast cancer (above 100 nanograms/mL) a daily dose of 800 mg of Provera is probably necessary in the presence of aminoglutethimide 125 or 250 mg twice daily. This is double the usual recommended dose for this condition. 

Aminoglutethimide 500 to 750 mg daily reduced the half-life of dexamethasone 1 mg from 264 to 120 minutes in 6 patients. In another 22 patients it was found that larger doses of dexamethasone (1.5 to 3 mg daily) compensated for the increased dexamethasone metabolism caused by aminoglutethimide and complete adrenal suppression was achieved over a prolonged period. Another study found a fourfold increase in dexamethasone clearance in 10 patients taking aminoglutethimide 1 g daily. ... 

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