Danazol

Danazol, 17a-pregna-2,4-dien-20-yno(2,3-d)-isoxazol-17-ol, is a synthetic steroid derived from ethisterone. Its pharmacological properties include:

1. Relatively marked affinity for androgen receptors, less marked affinity for progesterone receptors and least affinity for oestrogen receptors. Danazol is a weak androgen but in addition antiandrogenic, progestogenic, antiprogestogenic, oestrogenic and antioestrogenic actions have been observed.
2. Interference with the synthesis of gonadal steroids, possibly by inhibition of the enzymes of steroidogenesis, including 3β hydroxysteroid dehydrogenase,17β hydroxysteroid dehydrogenase, 17 hydroxylase, 17, 20 lyase, 11β hydroxylase, 21 hydroxylase and cholesterol side chain cleavage enzymes, or alternatively by inhibition of the cyclic AMP accumulation usually induced by gonadotrophic hormones in granulosa and luteal cells.
3. Inhibition of the mid-cycle surge of FSH and LH as well as alterations in the pulsatility of LH. Danazol can also reduce the mean plasma levels of these gonadotrophins after the menopause.
4. A wide range of actions on plasma proteins, including increasing prothrombin, plasminogen, antithrombin III, alpha-2 macroglobulin, C1 esterase inhibitor, and erythropoietin and reducing fibrinogen, thyroid binding and sex hormone binding globulins. Danazol increases the proportion and concentration of testosterone carried unbound in plasma.
5. The suppressive effects of danazol on the hypothalmic-pituitary-gonadal axis are reversible, cyclical activity reappearing normally within 60-90 days after therapy.

Danazol is absorbed from the gastrointestinal tract, peak plasma concentrations of 50-80ng/ml being reached approximately 2-3 hours after dosing. Compared to the fasting state, the bioavailability has been shown to increase 3 fold when the drug is taken with a meal with a high fat content. It is thought that food stimulates bile flow which facilitates the dissolution and absorption of danazol, a highly lipophilic compound.

The apparent plasma elimination half life of danazol in a single dose is approximately 3-6 hours. With multiple doses this may increase to approximately 26 hours.

None of the metabolites of danazol, which have been isolated, exhibits pituitary inhibiting activity comparable to that of danazol.

Few data on excretion routes and rates exist. In the monkey 36% of a radioactive dose was recoverable in the urine and 48% in the faeces within 96 hours.

No further data.