Dermovate Mechanism of Action

Pharmacotherapeutic Group: Corticosteroids, very potent (group IV). ATC code: D07AD.
Pharmacology: Pharmacodynamics: Mechanism of action: Topical corticosteroids act as anti-inflammatory agents via multiple mechanisms to inhibit late phase allergic reactions including decreasing the density of mast cells, decreasing chemotaxis and activation of eosinophils, decreasing cytokine production by lymphocytes, monocytes, mast cells and eosinophils, and inhibiting the metabolism of arachidonic acid.
Pharmacodynamic effects: Topical corticosteroids have anti-inflammatory, antipruritic, and vasoconstrictive properties.
Pharmacokinetics: Absorption: Topical corticosteroids can be systemically absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.
Mean peak plasma clobetasol propionate concentrations of 0.63 nanograms/ml occurred in one study eight hours after the second application (13 h after an initial application) of 30 g clobetasol propionate 0.05% ointment to normal individuals with healthy skin. Following the application of a second dose of 30 g clobetasol propionate cream 0.05%, mean peak plasma concentrations were slightly higher than the ointment and occurred 10 h after application. In a separate study, mean peak plasma concentrations of approximately 2.3 nanograms/ml and 4.6 nanograms/ml occurred respectively in patients with psoriasis and eczema three hours after a single application of 25 g clobetasol propionate 0.05% ointment.
Distribution: The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection.
Metabolism: Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver.
Elimination: Topical corticosteroids are excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.
Toxicology: Non-Clinical Information: Carcinogenesis/Mutagenesis: Carcinogenesis: Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.
Genotoxicity: Clobetasol propionate was not mutagenic in a range of in vitro bacterial cell assays.
Reproductive Toxicology: Fertility: In fertility studies, subcutaneous administration of clobetasol propionate to rats at doses of 6.25 to 50 micrograms/kg/day produced no effects on mating, and fertility was only decreased at 50 micrograms/kg/day.
Pregnancy: Subcutaneous administration of clobetasol propionate to mice (≥100 micrograms/kg/day), rats (400 micrograms/kg/day) or rabbits (1 to 10 micrograms/kg/day) during pregnancy produced foetal abnormalities including cleft palate and intrauterine growth retardation.
In the rat study, where some animals were allowed to litter, developmental delay was observed in the F1 generation at ≥100 micrograms/kg/day and survival was reduced at 400 micrograms/kg/day. No treatment-related effects were observed in F1 reproductive performance or in the F2 generation.