No metabolites of fluticasone propionate were detected in an in vitro study of radiolabeled fluticasone propionate incubated in a human skin homogenate. The total blood clearance of systemically absorbed fluticasone propionate averages 1,093 mL/min (range, 618 to 1,702 mL/min) after a 1-mg intravenous dose, with renal clearance accounting for less than % of the total. Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5- fluoromethyl carbothioate grouping. This transformation occurs in 1 metabolic step to produce the inactive17-ÃŸ-carboxylic acid metabolite, the only known metabolite detected in man. This metabolite has approximately 2,000 times less affinity than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.
Fluticasone propionate is a synthetic (man-made) corticosteroid that is used on the skin (topically). The naturally-occurring corticosteroid is cortisol or hydrocortisone produced by the adrenal gland. Corticosteroids have potent anti-inflammatory actions and also suppress the immune response. Similar drugs include betamethasone dipropionate (Diprolene), clobetasol propionate (Temovate), halobetasol propionate (Ultravate), betamethasone dipropionate (Diprosone), desoximetasone (Topicort), halcinonide (Halog), amcinonide (Cyclocort), triamcinolone acetonide (Kenalog), fluocinolone acetonide (Synalar), hydrocortisone butyrate (Locoid), hydrocortisone valerate (Westcort), and mometasone furoate (Elocon). The FDA approved topical fluticasone propionate in December, 1990.
Metyrapone is used for the medical control of hypercortisolism in Cushing's syndrome (ACTH dependent or independent). The aim for medical treatment is to achieve pre-operative control of hypercortisolism, or for control of residual disease persisting post-operatively (TSS, adrenalectomy). It is not for long term definitive treatment/cure, only as an adjunct (surgery is the aim for cure in most causes of Cushing's syndrome). Metyrapone hence acts by inhibiting adrenal steroidogenesis. One side effect is hirsutism (in women) because of the excess androgen precursors created. The other commonly used agent for medical treatment of Cushing's is ketoconazole (an anti-fungal agent). This does not exhibit the side effect of hirsutism.