In an open-label HPA axis safety trial in subjects 3 months to 12 years of age with atopic dermatitis, Betamethasone dipropionate cream (augmented), % was applied twice daily for 2 to 3 weeks over a mean body surface area of 58% (range 35% to 95%). In 19 of 60 (32%) evaluable subjects, adrenal suppression was indicated by either a ≤5 mcg/dL pre-stimulation cortisol, or a cosyntropin post-stimulation cortisol ≤18 mcg/dL and/or an increase of <7 mcg/dL from the baseline cortisol. Out of the 19 subjects with HPA axis suppression, 4 subjects were tested 2 weeks after discontinuation of Betamethasone dipropionate cream (augmented), % and 3 of the 4 (75%) had complete recovery of HPA axis function. The proportion of subjects with adrenal suppression in this trial was progressively greater, the younger the age group.
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.
Torsemide is administered orally and intravenously. It is metabolized by the hepatic cytochrome P450 enzyme system and is a substrate for CYP2C9. In humans, three metabolites, one of which is active, are produced. The active metabolite does not contribute significantly to clinical activity. In normal adults, about 80% is cleared through hepatic metabolism and 20% is cleared in the urine as unchanged drug. In healthy adults, the elimination half-life is about hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9
Torsemide is a substrate for CYP2C9. Theoretically, metabolism may be affected by drugs that are inhibitors of inducers of CYP2C9.