Desoximetasone (Desoximetasone Topical) - Description and Clinical Pharmacology

FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC USE.

Rx Only

DESCRIPTION

Desoximetasone Gel USP, 0.05% contains the active synthetic corticosteroid desoximetasone. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and anti-pruritic agents.

Each gram of Desoximetasone Gel USP, 0.05% contains 0.5 mg desoximetasone in a gel consisting of purified water USP, docusate sodium USP, edetate disodium USP, isopropyl myristate NF, carbomer 940, trolamine NF, SD alcohol 40 (20% w/w).

The chemical name of desoximetasone is Pregna-1, 4-diene-3, 20-dione, 9-fluoro-11, 21-dihydroxy-16-methyl-, (11β, 16α)-.

Desoximetasone has the empirical formula C₂₂H₂₉FO₄ and a molecular weight of 376.47.

The CAS Registry Number is 382-67-2.

The chemical structure is:

CLINICAL PHARMACOLOGY

Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/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

The extent of percutaneous absorption to topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids 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.

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. Corticosteroids are metabolized primarily in the liver and 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%) and no detectable level (limit of sensitivity: 0.005 µg/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. The half-life of the material was 15 ± 2 hours (for urine) and 17 ± 2 hours (for feces) between the third and fifth trial day.

Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester.