The effect of acetylator phenotype on the disposition of aminoglutethimide.

摘要: Aminoglutethimide (AG) 500 mg was administered orally to four normal volunteers and eight patients undergoing treatment for metastatic breast cancer. In each subject the acetylator phenotype established from monoacetyldapsone (MADDS)/dapsone (DDS) ratio. Acetylaminoglutethimide (acetylAG) rapidly appeared in plasma its disposition paralleled that of AG. A close relationship (P less than 0.01) observed between acetyl AG/AG MADDS/DDS ratio suggesting AG may undergo polymorphic acetylation like DDS. half-life 19.5 +/- 7.7 h seven fast acetylators DDS 12.6 2.3 five slow apparent metabolic clearance significantly related acetylAG/AG Over 48 excreted 4.4% dose urine as unchanged compared 12.4 2.8% acetylators. much smaller fraction acetylAG: 3.6 1.5% by 1.9 1.0% respectively. After 7 days with at an accepted clinical regimen there were significant reductions half-lives acetylAG a trend (0.1 greater P 0.05) towards reduction which became if one patient on known enzyme inducer omitted. The mean volume distribution not 0.1) altered but systemic increased 0.05). These changes are attributed auto-induction oxidative enzymes involved metabolism.