Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic Group: D10A Anti-Acne Preparations for Topical Use 
ATC code: D10AD03

Adapalene is a retinoid-like compound which in, in vivo and in vitro models of inflammation, has been demonstrated to possess anti-inflammatory properties.
Adapalene is essentially stable to oxygen and light and is chemically non-reactive.
Mechanically, adapalene binds like tretinoin to specific retinoic acid nuclear receptors but, unlike tretinoin not to cytosolic receptor binding proteins.
Adapalene applied cutaneously is comedolytic in the rhino mouse model and also has effects on the abnormal processes of epidermal keratinisation and differentiation, both of which are present in the pathogenesis of acne vulgaris. The mode of action of adapalene is suggested to be a normalisation of differentiation of follicular epithelial cells resulting in decreased microcomedone formation.

Adapalene is superior to reference retinoids in standard anti-inflammatory assays, both in vivo and in vitro. Mechanistically, it inhibits chemotactic and chemokinetic responses of human polymorphonuclear leucocytes and also the metabolism by lipoxidation of arachidonic acid to pro-inflammatory mediators. This profile suggests that the cell mediated inflammatory component of acne may be modified by adapalene. Studies in human patients provide clinical evidence that cutaneous adapalene is effective in reducing the inflammatory components of acne (papules and pustules).

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption of adapalene through human skin is low, in clinical trials measurable plasma adapalene levels were not found following chronic cutaneous application to large areas of acneic skin with an analytical sensitivity of 0.15 ng/ml.

After administration of [14C]-adapalene in rats (IV, IP, oral and cutaneous), rabbits (IV, oral and cutaneous) and dogs (IV and oral), radioactivity was distributed in several tissues, the highest levels being found in liver, spleen, adrenals and ovaries.
Metabolism in animals has been tentatively identified as being mainly by O- demethylation, hydroxylation and conjugation, and excretion is primarily by the biliary route.