Metabolites of danazol (17 alpha-pregna-2,4-dien-20-yno[2,3-d]isoxazol-17-ol), an orally effective pituitary gonadotropin inhibitory agent devoid of estrogenic and progestational activites, were isolated from urine of a female subject who had taken danzol orally at a dose of 800 mg/day for 7 days, The metabolites isolated were 17-hydroxy-17alpha-pregn-4-en-20-yn-3-one (11), 17-hydroxy-2alpha-(hydroxymethyl)-17alpha-pregn-4-3n-20-yn-3-one (5), 17-hydroxy-2-(hydroxymethyl)-17alpha-pregna-1,4-dien-20-yn-3-one(7), 6beta,17-dihydroxy-2alpha-(hydroxymethyl)-17alphapregn-4-en-20-yn-3-one(8), and 6beta, 17-dihydroxy-2(hydroxymethyl)-17alphapregna-1,4-dien-20yn-3-one(10). None of these metabolites exhibited pituitary inhibiting activity comparable to danazol.
PIP: Urinary metabolites of danazol (17alpha-pregna-2,4-dien-20-yno (2,3-delta)isoxazol-17-01), and inhibitor of pituitary gonadotropins, were isolated from a woman who had been taking the drug orally at a dose of 800 mg/day for 7 days. The isolated metabolites were 17-hydroxy-17alpha-pregn-4-en-20-yn-3-one, 17-hydroxy-2alpha-(hydroxymethyl)-17alpha-pregn-4-en-20-yn-3-one, 47-hydroxy-2-(hydroxymethyl)-17alpha-pregna-1,4-dien-20-yn-3-one, 6beta,17-dihydroxy-2alpha-(hydroxymethyl)-17alpha-pregn-4-en-20-yn-3-one and 6beta,17-dihydroxy-2-(hydroxymethyl)-17alpha-pregna-1,4-dien-20-yn-3-one. The pituitary inhibiting activity of these metabolites was less than that of danazol.