Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties

Pharmacotherapeutic group: Corticosteroids, very potent (group IV) ATC code: D07AD

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.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

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 ng/ml occurred in one study eight hours after the second application (13 hours 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 hours after application.

In a separate study, mean peak plasma concentrations of approximately 2.3 ng/ml and 4.6 ng/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.