The broad objective of the proposed studies is to provide physicochemical baselines for the design of new, better performing topical antibacterials and antibiotics for burn victims, and for the design of better performing formulations for such agents, and for the more rational clinical deployment of the therapeutics presently used to control burn wound sepsis. The early studies are aimed at developing suitable methodology in appropriate animal systems for the quantitative study of the permeability of burned skin (eschar) and at obtaining firm eschar permeability data using the developed procedures. The data generated will be used to delineate the general barrier properties of the burned skin surface and to develop quantitative integrated models for describing the release of drugs from topical applications and the subsequent tissue and systemic adsorption. Basic eschar permeability data will be obtained for model homologous and otherwise systematically altered compounds in order to pin down the operational physicochemical mechanism for absorption and pinpoint physiological and physicochemical factors critical to drug bioavailability. The studies will also involve estimation of the intrinsic permeation rates of select topical antibiotics and antiseptics and the influences of intensity of the burn and maturation of the burn on permeability.