Halovate Mechanism of Action

Pharmacology: Like other topical corticosteroids, Halobetasol propionate has anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of the anti-inflammatory activity of the topical corticosteroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier. Occlusive dressings with hydrocortisone for up to 24 hours have not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Human and animal studies indicate that less than 6% of the applied dose of Halobetasol propionate enters the circulation within 96 hours following topical administration of Halobetasol propionate.
Studies performed with Halobetasol propionate indicate that it is in the super-high range of potency as compared with other topical corticosteroids.
Nonclinical Toxicology: Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential of Halobetasol propionate. Positive mutagenicity effects were observed in two genotoxicity assays. Halobetasol propionate was positive in a Chinese hamster micronucleus test, and in a mouse lymphoma gene mutation assay in vitro.
Studies in the rat following oral administration at dose levels up to 50 mcg/kg/day indicated no impairment of fertility or general reproductive performance.
In other genotoxicity testing, Halobetasol propionate was not found to be genotoxic in the Ames/Salmonella assay, in the sister chromatid exchange test in somatic cells of the Chinese hamster, in chromosome aberration studies of germinal and somatic cells of rodents, and in a mammalian spot test to determine point mutations.