Aminoglutethimide as an inducer of microsomal enzymes. Part 2: Endocrine aspects.
Using a [4-14C]estradiol bolus injection technique possible effects of AG administration on estrogen metabolism were studied in seven patients. No alterations in steroid disposition were seen after a short term AG treatment. Chronic AG administration produced no change in mean estradiol clearance value. Chronic AG treatment as a low- or high-dose drug schedule produced a consistent reduction in estrone sulfate production rate (mean reductions 24 and 42%) as well as an increased estrone sulfate elimination rate constant (mean increase 30 and 69%). Urinary estriol secretion rate was consistently increased during chronic treatment (mean increase 95%) with no difference between low- and high dose drug schedules. These findings are consistent with AG being a potent enzyme inducer stimulating estrogen metabolism, and this mechanism may be an important part of AG mechanism of action by reducing estrone sulfate bioavailability.
D000616:Aminoglutethimide / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism* / Q000652:urine; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D008593:Menopause; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*
D004967:Estrogens; D000616:Aminoglutethimide; D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate