Utility of a Three-Dimensional Cultured Human Skin Model as a Tool to Evaluate the Simultaneous Diffusion and Metabolism of Ethyl Nicotinate in Skin

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  The simultaneous diffusion and metabolism of ethyl nicotinate (EN) in a cultured human skin model, Living Skin Equivalent-high, was evaluated by the in vitro skin permeation and metabolism experiments, and esterase distribution was also determined. Theoretical calculations using Fick's 2nd Law of Diffusion with Michaelis-Menten kinetics were performed to obtain the permeation and metabolic parameters together with information on enzyme distribution. The obtained data was compared with the corresponding results in excised hairless rat skin. The partition coefficient of EN from the vehicle to the skin was of the same order of magnitude for the cultured human skin and hairless rat skin, but the diffusion and metabolic parameters were different. Esterase concentration in the epidermal membrane was greater than in the dermis of cultured skin, which was similar to hairless rat skin. Taking into account the similarities and differences between the membranes, the cultured human skin model can be utilized as a model membrane to rapidly predict simultaneous diffusion and metabolism of the prodrug through human skin.<br>

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