Klenzit-MS Mechanism of Action

Pharmacotherapeutic Group: D10A Anti-Acne Preparations for Topical Use. ATC code: D10AD03.
Pharmacology: Pharmacodynamics: 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 keratinization 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.
Microsponge delivery system of microspheres: Microsponge is a polymeric delivery system consisting of solid phase porous microspheres, which are round microscopic particles made of synthetic polymer. These particles entrap the active drug, Adapalene, in the microsponge system. After the product is applied, the entrapped drug is then delivered to the skin in a controlled time-release pattern or a pre-programmed manner after it has been applied to the skin.
The microsphere hold the drug in reserve, allowing the skin to absorb small amounts of active drug over time, thereby reducing irritation or almost no irritation because microspheres themselves remain on top of the skin and are easily washed off when the patient takes a shower or washes the face.
Although the microsponge size may vary usually from 5 to 300 μm in diameter, a typical 25 μm sphere can have up to 250,000 pores and an internal pore structure equivalent to 10 ft. in length, providing a total pore volume of about 1 mL/g. This results in a large reservoir within each Microsponge, which can be loaded with up to its own weight in active agents.
Adapalene microsphere formulation contains 3 to 10 μm sized microparticles of Adapalene entrapped in microspheres less than 150 μm in diameter.
The penetration properties of the microspheres in the skin depend on the size of the particles. Rolland et al (1993) and other studies have reported that microspheres of 310 μm, topically applied to human skin, aggregated in the follicular orifices and pilosebaceous unit. Adapalene microparticles enter selectively into the hair follicle and may yield high local concentrations of the active compound. The controlled destabilization of the microspheres may allow a controlled release of drug and thus provides a highly selective, specific and potent action at the target without irritating the other tissues.
Pharmacokinetics: The pharmacokinetics of topical Adapalene has not been extensively studied. Therapeutic effects of the drug usually appear within 8 to 12 weeks of initiation of treatment. The transdermal absorption of Adapalene is low. Only trace amounts of the parent substance (<0.25 ng/mL) have been found in the plasma of acne patients following chronic topical application of Adapalene gel in controlled clinical trials. The micro particles of Adapalene, being of the size of 3 to 10 μm, achieve follicular targeting and action at the pilosebaceous unit without dispersing into the corneum and causing irritation. Thus enhanced effect as well as safety is achieved with Adapalene microsponge delivery. Excretion of any systemically absorbed Adapalene appears to be primarily by the biliary route.