Dermatokinetics: Advances and Experimental Models, Focus on Skin Metabolism

Curr Drug Metab. 2022 May 17. doi: 10.2174/1389200223666220517114004. Online ahead of print.ABSTRACTNumerous dermal contact products, such as drugs or cosmetics, are applied on the skin, the first protective barrier to their entrance into the organism. These products contain various xenobiotic molecules that can penetrate the viable epidermis. Many studies have shown that keratinocyte metabolism could affect their behavior by biotransformation. While aiming for detoxification, toxic metabolites can be produced. These metabolites may react with biological macromolecules often leading to sensitization reactions. After passing through the epidermis, xenobiotics can reach the vascularized dermis and therefore be bioavailable and distributed into the entire organism. To highlight these mechanisms, dermatokinetics, based on the concept of pharmacokinetics, has been developed recently. It provides information on the action of xenobiotics that penetrate the organism through the dermal route. The purpose of this review is first to describe and synthesize the dermatokinetics mechanisms to consider when assessing the absorption of a xenobiotic through the skin. We focus on skin absorption and specifically on skin metabolism, the two main processes involved in dermatokinetics. In addition, experimental models and methods to assess dermatokinetics are described and discussed to select the most relevant method when evaluating, in a specific context, dermatokinetics parameters of a xenobiot...
Source: Current Drug Metabolism - Category: Drugs & Pharmacology Authors: Source Type: research