Clobetasol propionate

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The precise mechanism of the anti-inflammatory activity of topical steroids in the treatment of steroid-responsive dermatoses, in general, is uncertain. However, corticosteroids are thought to act by the induction of phospholipase A₂ 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.

Pharmacodynamic effects

A vasoconstrictor study has shown that clobetasol propionate cutaneous foam has a comparable potency, based upon skin blanching response, as other clobetasol propionate formulations.

Absorption and distribution

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the carrier, the integrity of the epidermal barrier, the severity of the disease and the area treated. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption.

Topical corticosteroids can be absorbed from intact healthy skin.

Metabolism and elimination

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolised, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

In a controlled pharmacokinetic study, 3 of 13 subjects experienced reversible suppression of the adrenals at any time during the 14 days of clobetasol propionate cutaneous foam therapy to at least 20% of the body surface area.

Non-clinical data reveal no special hazard for humans based on studies of repeated dose toxicity and genotoxicity. No topical studies were performed to assess the safety, pharmacology and the carcinogenic potential of clobetasol.

Parenteral administration of corticosteroids, including clobetasol propionate, to pregnant animals can cause abnormalities of foetal development including cleft palate and intrauterine growth retardation. Animal studies have indicated that intrauterine exposure to corticosteroids may contribute to the development of cardiovascular and metabolic diseases in adult life, but there is a lack of evidence for the occurrence of such effects in humans.

In fertility studies, subcutaneous administration of clobetasol propionate to rats at doses of 6.25 to 50 micrograms/kg/day produced no effects on male fertility. In females, increased embryofetal loss and growth suppression and thymic atrophy in the litters were observed at the highest dose.