Corticosteroids have been used as drug treatment for some time. Lewis Sarett of Merck & Co. was the first to synthesize cortisone, using a complicated 36-step process that started with deoxycholic acid, which was extracted from ox bile .  The low efficiency of converting deoxycholic acid into cortisone led to a cost of US $200 per gram. Russell Marker , at Syntex , discovered a much cheaper and more convenient starting material, diosgenin from wild Mexican yams . His conversion of diosgenin into progesterone by a four-step process now known as Marker degradation was an important step in mass production of all steroidal hormones, including cortisone and chemicals used in hormonal contraception .  In 1952, . Peterson and . Murray of Upjohn developed a process that used Rhizopus mold to oxidize progesterone into a compound that was readily converted to cortisone.  The ability to cheaply synthesize large quantities of cortisone from the diosgenin in yams resulted in a rapid drop in price to US $6 per gram, falling to $ per gram by 1980. Percy Julian's research also aided progress in the field.  The exact nature of cortisone's anti-inflammatory action remained a mystery for years after, however, until the leukocyte adhesion cascade and the role of phospholipase A2 in the production of prostaglandins and leukotrienes was fully understood in the early 1980s.
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.
IMPORTANT SAFETY INFORMATION
Indication : TRI‐LUMA ® Cream is indicated for the short‐term (up to 8 weeks) treatment of moderate to severe melasma of the face in the presence of measures for sun avoidance, including the use of sunscreens. Adverse Events : In the controlled clinical trials, the most frequently reported events were redness, peeling, burning, dryness, and itching at the site of application. Warnings/Precautions : TRI‐LUMA contains sulfites which may cause severe, life‐threatening allergic reactions in people allergic to sulfites. TRI‐LUMA contains hydroquinone, which may cause a gradual blue‐black darkening of the skin. If you are pregnant, nursing or trying to become pregnant you should not use TRI‐LUMA. Safety and efficacy have not been established in individuals with darker skin. Reversible HPA axis (adrenal function) suppression may result from exposure to the topical corticosteroid, fluocinolone acetonide, so discontinue use if signs and symptoms of this condition occur. Avoid products that may dry or irritate the skin, such as abrasive cleansers, scrubs, or skin‐peeling agents. Exposure to sunlight, sunlamps, or UV light and extreme heat, wind, or cold should be avoided. If exposure cannot be avoided, sunscreen products [SPF 30 or more] and protective apparel should be used.
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