Temovate E (Clobetasol Propionate Topical (Emollient)) - Description and Clinical Pharmacology

DESCRIPTION

Temovate^® E (clobetasol propionate) Cream, 0.05% contains the active compound clobetasol propionate, a synthetic corticosteroid, for topical use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity.

Chemically, clobetasol propionate is (11β,16β)-21-chloro-9-fluoro-11-hydroxy-16-methyl-17-(1-oxopropoxy)-pregna-1,4-diene-3,20-dione, and it has the following structural formula:

Clobetasol propionate has the molecular formula C₂₅H₃₂ClFO₅ and a molecular weight of 467. It is a white to cream-colored crystalline powder insoluble in water.

Each gram of Temovate^® E contains 0.5 mg of clobetasol propionate in a white to off-white cream base consisting of cetostearyl alcohol, isopropyl myristate, propylene glycol, cetomacrogol 1000, dimethicone 360, citric acid, sodium citrate, purified water, and imidurea as a preservative.

CLINICAL PHARMACOLOGY

Mechanism of Action

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. 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.

Pharmacodynamics

Temovate^® E is in the super-high range of potency as demonstrated in a vasoconstrictor study in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

NONCLINICAL TOXICOLOGY

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis
Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.

Mutagenesis
Clobetasol propionate was nonmutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. Coli B WP2 fluctuation test.

Impairment of Fertility
Studies in the rat following oral administration at dosage levels up to 50 mg/kg per day revealed no significant effect on the males. The females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

CLINICAL STUDIES

In a controlled clinical trial involving patients with moderate to severe plaque-type psoriasis, Temovate^® E was applied to 5% to 10% of body surface area. In this trial, there were no clobetasol-treated patients with clinically significant decreases in morning cortisol levels after 4 weeks of treatment; however, morning cortisol levels may not identify patients with adrenal dysfunction.