Desonate (Desonide Topical) - Description and Clinical Pharmacology

DESCRIPTION

Desonate Gel contains desonide (pregna-1,4-diene-3, 20-dione,11, 21-dihydroxy-16, 17-[(1-methylethylidene) bis(oxy)]-, (11ß,16α)- a synthetic nonfluorinated corticosteroid for topical dermatologic use. Chemically, desonide is C₂₄H₃₂O₆. It has the following structural formula:

Desonide has the molecular weight of 416.52. It is a white to off-white odorless powder which is soluble in methanol and practically insoluble in water.

Each gram of Desonate Gel contains 0.5 mg of desonide in an aqueous gel base of purified water, glycerin, propylene glycol, edetate disodium dihydrate, methylparaben, propylparaben, sodium hydroxide, and Carbopol^® 981.

CLINICAL PHARMACOLOGY

Topical corticosteroids share 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.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including product formulation and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption. Topical corticosteroids can be absorbed from normal intact skin. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolized primarily in the liver and then are excreted by the kidneys. Some corticosteroids and their metabolites are also excreted in the bile.

In a controlled pharmacokinetic study, one of 37 (3%) pediatric subjects with moderate to severe atopic dermatitis covering at least 35% body surface area who applied Desonate Gel experienced suppression of the adrenal glands following 4 weeks of therapy (see PRECAUTIONS: General and Pediatric Use). A follow-up evaluation of the subject’s adrenal axis was not performed; it is unknown whether the suppression was reversible.

CLINICAL STUDIES

In two randomized vehicle-controlled clinical studies, patients 3 months to 18 years of age with mild to moderate atopic dermatitis were treated twice daily for 4 weeks with either Desonate Gel or vehicle. Treatment success was defined as achieving clear or almost clear on the Investigator’s Global Severity Score (IGSS) with at least a 2 point change (decrease) from the subject’s baseline IGSS when compared to the Week 4 IGSS. The results of the 2 clinical trials are summarized in Table 1:

Table 1. Subjects Achieving Treatment Success

Clinical Trial 1		Clinical Trial 2
Desonate  Gel	Vehicle	Desonate  Gel	Vehicle
N = 289	N = 92	N = 136	N = 65
128 (44%)	13 (14%)	38 (28%)	4 (6%)