Metabolism of aminoglutethimide in humans: quantification and clinical relevance of induced metabolism.
Hydroxylaminoglutethimide [3-ethyl-3-(4-hydroxylaminophenyl)piperidine-2,6-dione] (HxAG), aminoglutethimide [3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione] (AG) and N-acetyl-aminoglutethimide (N-AcAG) have been quantified by high performance liquid chromatography using m-aminoglutethimide (metaAG) as the internal standard in serial 24 h urine collections from a patient on chronic AG therapy without steroid supplementation. HxAG is the product of a major AG-induced metabolic pathway since the ratio [HxAG]/[AG] rises with time. In contrast the ratio [N-AcAG]/[AG] decreases with time. A rapid, simple colorimetric assay has been used to quantify HxAG in urine from both male and female patients receiving a range of doses of AG and to show that induced metabolism is a general phenomenon even at low doses (125 mg twice daily). AG therapy is known to alter the metabolic rate and plasma half-life of a number of coadministered compounds including dexamethasone and warfarin. Clinicians should remain alerted to this phenomenon.
D000616:Aminoglutethimide / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use / Q000652:urine; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003124:Colorimetry; D005260:Female; D006801:Humans; D008297:Male
D000616:Aminoglutethimide; C040419:hydroxylaminoglutethimide