Teracorte Mechanism of Action

Pharmacology: Pharmacodynamics: Topical corticosteroids share anti-inflammatory, antipruritic, and vasoconstrictive actions. The mechanism of anti-inflammatory activity of desoximetasone is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.
Pharmacokinetics: Absorption: The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Desoximetasone can be absorbed from normal, intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. There was no detectable level (limit of sensitivity: 0.005 mcg/mL) in the blood when it was applied topically on the back followed by occlusion for 24 hours. Seven days after application, no further radioactivity was detected in urine or feces. Pharmacokinetic studies in men with desoximetasone ointment 0.25% with tagged desoximetasone showed no detectable level (limit of sensitivity: 0.003 mcg/mL) in 1 subject and 0.004 and 0.006 mcg/mL in the remaining 2 subjects in the blood when it was applied topically on the back followed by occlusion for 24 hours. The extent of absorption for the ointment was 7% based on radioactivity was detected in urine and feces. Seven days after application, no further radioactivity recovered from the urine or feces. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.
Distribution: Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees.
Metabolism: Corticosteroids are metabolized primarily in the liver.
Excretion: They are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile. Pharmacokinetic studies in men with desoximetasone cream 0.25% with tagged desoximetasone showed a total of 5.2% ± 2.9% excretion in urine (4.1% ± 2.3%) and feces 1.1% ± 0.6%). The half-life of the material was 15 ± 2 hours (for urine) and 17 ± 2 hours (for feces) between the 3^rd and 5^th trial day.