Potentiated by CYP3A4 inhibitors (eg, ketoconazole, macrolides), cyclosporine, estrogens. Antagonized by CYP3A4 inducers (eg, barbiturates, phenytoin, carbamazepine, rifampin), cholestyramine. May potentiate cyclosporine (seizure risk). May antagonize oral anticoagulants (monitor), isoniazid. Increased risk of arrhythmias with digitalis. May need to adjust dose of antidiabetic agents. Monitor for hypokalemia with potassium-depleting drugs (eg, amphotericin B, diuretics). Concomitant neuromuscular blocking agents; increased risk of myopathy. Withdraw anticholinesterase agents at least 24hrs before initiating corticosteroid therapy. Aminoglutethimide may lead to loss of corticosteroid-induced adrenal suppression. Increased GI effects with aspirin, other NSAIDs. Caution with aspirin in hypoprothrombinemia. May suppress reactions to skin tests.
Dexamethasone is absorbed rapidly after oral administration with a half-life of about 190 minutes. Sufficient absorption may occur after topical application to the skin and eye to produce systemic effects. In plasma dexamethasone protein binding is less than for most other corticosteroids. Corticosteroids diffuse into tissue fluids and cerebrospinal fluid but transplacental diffusion in significant amounts has not been demonstrated. Corticosteroids are metabilised in the liver the kidney and excrete in the urine. Metabolism is similar to other corticosteroids. Intraocular penetration occurs in significant amounts and contributes to the effectiveness of dexamethasone in anterior segment inflammatory disease.
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.