Comparison of the pharmacokinetics and pharmacodynamics of unformulated and formulated 4-hydroxyandrostenedione taken orally by healthy men

Cancer Chemotherapy and Pharmacology
M Dowsett, P Lloyd

Abstract

A study of the aromatase inhibitor 4-hydroxy-androstenedione (4-OHA) was conducted in normal healthy men to compare the oral administration of two preparations of the drug: an unformulated, micronized powder and a formulated microcrystalline material (CGP 32349). The formulated material achieved a significantly higher mean peak concentration (88% greater than that obtained using the unformulated powder) and a higher mean AUC (not significant). The median time to peak was 1.5 h for both preparations and the elimination rate constants were similar (0.31 for micronized 4-OHA and 0.36 h-1 for formulated 4-OHA). Plasma concentrations of 4-OHA in this group were markedly lower than those previously observed in postmenopausal breast cancer patients. Significant biological activity was demonstrated with the formulated material in its suppression of plasma oestradiol levels, whereas no significant suppression was obtained using the micronized powder. An increase in androgen levels was observed that may have been due to competitive inhibition of enzymes involved in metabolic clearance of androgens and/or to decreased feedback inhibition of gonadotrophin secretion by oestradiol.

References

Jan 1, 1987·Cancer Chemotherapy and Pharmacology·D CunninghamR C Coombes
Dec 1, 1971·The Journal of Clinical Endocrinology and Metabolism·R J SantenC A Paulsen
Oct 1, 1982·The Journal of Clinical Endocrinology and Metabolism·A L HarrisI E Smith
May 1, 1983·British Journal of Cancer·A L HarrisS L Jeffcoate
Dec 1, 1984·The Journal of Clinical Endocrinology and Metabolism·W E EllinwoodJ A Resko
Sep 1, 1982·Annals of Clinical Biochemistry·K M FergusonS L Jeffcoate

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Citations

Jan 1, 1994·Breast Cancer Research and Treatment·M Dowsett, R C Coombes
Dec 20, 1990·The Journal of Steroid Biochemistry and Molecular Biology·M Dowsett
May 19, 2001·The Journal of Steroid Biochemistry and Molecular Biology·P E LønningJ W Faigle
Jul 8, 2003·Clinical Pharmacokinetics·Per Lønning
Feb 23, 2012·Drug Testing and Analysis·Thomas PiperMartial Saugy
Jan 1, 1992·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M DowsettR C Coombes

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