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Pharmacology: Pharmacokinetics: Absorption: Blood levels of danazol do not increase proportionately with increase in dose. When the dose is doubled, plasma levels increase only approximately 35% to 40%. Bioavailability and peak plasma concentrations of danazol increased by 3- to 4-fold, respectively, in healthy woman who received 100- and 200-mg of danazol as single doses with a high-fat meal (more than 30 g of fat) compared with those who received the drug under fasting conditions. In addition, administration with food delayed mean time to reach peak plasma danazol concentrations by about 30 minutes.
Distribution and Elimination: Danazol is metabolized to 2-hydroxy-methylethisterone, which appears in the plasma in a concentration 5-10 times greater than that of the unchanged drug.
Pharmacodynamics: Danazol is a synthetic derivative of ethisterone (ethinyl testosterone) with weak androgenic and anabolic properties and no estrogenic or progestrogenic activity. Danazol suppresses the pituitary-ovarian axis by inhibiting the output of pituitary gonadotropins. It also has weak, androgenic activity. Danazol depresses the output of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). There is evidence that danazol directly inhibits the synthesis of sex steroids and binds to gonadal (sex) steroid receptors in the cytoplasm of target tissues and may thereby exhibit antiestrogen, anabolic, and weakly androgenic effects. The drug possesses weak androgenic and anabolic properties but exerts no estrogenic or progestogenic activities; androgenic activity is dose related. In addition, danazol has been shown to significantly decrease IgG, IgM, and IgA levels, as well as phospholipid and IgG isotope autoantibodies in patients with endometriosis and associated elevations of autoantibodies. Generally, the pituitary suppressive action is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days after therapy is discontinued.
Endometriosis: In the treatment of endometriosis, danazol alters the normal and ectopic endometrial tissue so that it becomes inactive and atrophic. Complete resolution of endometrial lesions occurs in the majority of cases. Changes in vaginal cytology and cervical mucus reflect the suppressive effect of danazol on the pituitary-ovarian axis.
Hereditary Angioedema: Danazol prevents attacks of the disease characterized by episodic edema of the abdominal viscera, extremities, face, and airway that may be disabling and, if the airway is involved, fatal. In addition, danazol partially or completely corrects the primary biochemical abnormality of hereditary angioedema. It increases the levels of the deficient C1 esterase inhibitor, thereby increasing the serum levels of the C4 component of the complement system.
