SKIN PENETRATION AND METABOLISM - COMPARATIVE-EVALUATION OF SKIN EQUIVALENT, CELL-CULTURE, AND HUMAN SKIN

Using an organotypic model of human skin, living skin equivalent (LSE) and its homogenate, monolayer cell culture, and human skin, we have studied the simultaneous transport and metabolic fate of two compounds. The LSE was maintained in an assay culture medium. When the model compounds were applied to LSE at dosages of 9.0 +/- 1.2 mug/cm2, the transport of salicylic acid through human skin was 0.12 +/- 0.1 mug/cm2/hr. Salicylic acid flux was 5.6-fold greater in LSE than in human skin. Shorter lag time of absorption was observed in LSE (approximately 1.5 hr) than in human skin (7-9 hr). Percutaneous transport across LSE was accompanied by metabolism of the compounds and there were quantitative and qualitative similarities between the metabolites produced by the LSE and human skin. When compounds were added to homogenates (LSE or skin) and to human cell cultures, the activities of the LSE and human fractions were similar. Data from the present study demonstrate that although LSE is more permeable than human skin, the artificial skin is a potentially valuable model for skin pharmacologic studies.