Cytochrome p450: a target for drug development for skin diseases

Enzymes of the cytochrome P450 (P450 or CYP) super family are the most versatile and important class of drug-metabolizing enzymes that are induced in mammalian skin in response to xenobiotic exposure. At the same time, CYP have numerous important roles in endogenous and exogenous substrate metabolism in the skin. For example, they participate in the metabolism of therapeutic drugs, fatty acids, eicosonoids, sterols, steroids, vitamin A, and vitamin D, to name a few. In addition, in some skin diseases, for example in psoriasis, many CYP are elevated. CYP are the target of special interest in the development of drugs for skin diseases because most, if not all, drugs available in the armamentarium of the dermatologists are either substrate, inducer, or inhibitor of this enzyme family. The functional significance of drug metabolism in skin and the implication of CYP in skin pathology and therapy is an area for future investigation. A detailed insight into the mechanism of action of various cutaneous CYP, being capable of modulating the drug bioavailability, will be helpful in the development of better strategies for novel therapy against constantly increasing skin disorders. This brief review discusses some of these perspectives and suggests additional work in this research area with regard to the expression and modulation of CYP in mammalian skin as well as their implication in dermatological disorders and the therapy of skin diseases.