Abstract
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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Coombes R. C., Chilvers C., Dowsett M., Gazet J. C., Ford H. T., Bettelheim R., Gordon C., Smith I. E., Zava D., Powles T. J. Adjuvant aminoglutethimide therapy for postmenopausal patients with primary breast cancer: progress report. Cancer Res. 1982 Aug;42(8 Suppl):3415s–3419s. [PubMed] [Google Scholar]
- Coombes R. C., Foster A. B., Harland S. J., Jarman M., Nice E. C. Polymorphically acetylated aminoglutethimide in humans. Br J Cancer. 1982 Sep;46(3):340–345. doi: 10.1038/bjc.1982.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Foster A. B., Jarman M., Leung C. S., Rowlands M. G., Taylor G. N. Analogues of aminoglutethimide: selective inhibition of cholesterol side-chain cleavage. J Med Chem. 1983 Jan;26(1):50–54. doi: 10.1021/jm00355a011. [DOI] [PubMed] [Google Scholar]
- Jarman M., Foster A. B., Goss P. E., Griggs L. J., Howe I., Coombes R. C. Metabolism of aminoglutethimide in humans: identification of hydroxylaminoglutethimide as an induced metabolite. Biomed Mass Spectrom. 1983 Nov;10(11):620–625. doi: 10.1002/bms.1200101108. [DOI] [PubMed] [Google Scholar]
- Lønning P. E., Kvinnsland S., Jahren G. Aminoglutethimide and warfarin. A new important drug interaction. Cancer Chemother Pharmacol. 1984;12(1):10–12. doi: 10.1007/BF00255901. [DOI] [PubMed] [Google Scholar]
- Murray F. T., Santner S., Samojlik E., Santen R. J. Serum aminoglutethimide levels: studies of serum half-life, clearance, and patient compliance. J Clin Pharmacol. 1979 Nov-Dec;19(11-12):704–711. doi: 10.1002/j.1552-4604.1979.tb01640.x. [DOI] [PubMed] [Google Scholar]
- Powles T. J., Gordon C., Coombes R. C. Clinical trial of multiple endocrine therapy for metastatic and locally advanced breast cancer with tamoxifen-aminoglutethimide-danazol compared to tamoxifen used alone. Cancer Res. 1982 Aug;42(8 Suppl):3458s–3460s. [PubMed] [Google Scholar]
- Santen R. J., Wells S. A., Runić S., Gupta C., Kendall J., Rudy E. B., Samojlik E. Adrenal suppression with aminoglutethimide. I. Differential e-fects of aminoglutethimide on glucocorticoid metabolism as a rationale for use of hydrocortisone. J Clin Endocrinol Metab. 1977 Sep;45(3):469–479. doi: 10.1210/jcem-45-3-469. [DOI] [PubMed] [Google Scholar]