Dermatokinetics: Advances and Experimental Models, Focus on Skin Metabolism

Paul      Quantin; Mathilde      Stricher; Sophie      Catoire; Hervé      Ficheux; Christophe      Egles
doi:10.2174/1389200223666220517114004
Abstract

Numerous 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 xenobiotic. We also discuss the limits of this approach as it is notably used for risk assessment in the industry where scenario studies generally focus only on one xenobiotic and do not consider interactions with the rest of the exposome. The hypothesis of adverse effects due to the combination of chemical substances in contact with individuals and not to a single molecule, is being increasingly studied and embraced in the scientific community.
Keywords: In vitro models, toxicity, metabolism, drugs, xenobiotics, dermatokinetics.
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DOI https://dx.doi.org/10.2174/1389200223666220517114004	Print ISSN 1389-2002
Publisher Name Bentham Science Publisher	Online ISSN 1875-5453
Current Drug Metabolism

Dermatokinetics: Advances and Experimental Models, Focus on Skin Metabolism

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