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Estimation of Skin Absorption of Chemicals to Evaluate Systemic Exposure

The skin forms a barrier between the body and the environment, preventing water loss and penetration of exogenous substances, and upholds homeostasis. The prevention of exogenous substance penetration a priori indicates that a passage of either toxic or medicinal compounds through the skin represents very important problem for topical drug development and application. The topical drugs are developed to deliver an active molecule either to a certain compartment in the skin or through the skin to peripheral blood circulation. In both cases, the pharmacological activity is determined by drug concentration, either in skin or in blood. The efficiency and efficacy of topical drug delivery to peripheral blood circulation is judged by the blood concentration of a drug. Moreover, the blood concentration-time course can be predicted using skin permeation parameters obtained from the invitro skin permeation experiments. Thus, skin permeation experiments are very important to assess systemic exposure of chemicals. Synthetic membranes and three-dimensional cultured human skin models have been utilized for in vitro skin permeation experiments as alternative membranes, especially in the development of cosmetic products. Furthermore, recently, in silico perdiction of absorbed drug after topical application have been developed. In this presentation, usefulness of estimation of skin absorption with synthetic menbrane as well as insilico model would be introduced. I hope this presentation would be helpful for estimation of skin absorption of chemicals to assess systemic exposure.