We are examining the potential of the oral mucosa as a systemic portal for new therapeutic agents such as peptide drugs which are currently being developed. As part of this effort, we hope to be able to derive predictive algorithms that can be used to estimate the rate and extent of a compound's absorption through the oral mucosa. Neither theoretical nor experimental prediction of oral mucosal penetration kinetics is generally established (although there have been some intriguing recent efforts to do so. Thus there exists no reliable way to estimate the rate and extent of transmuscosal permeation from a dosage form that adheres to the tissue, apart from the unfeasible alternative of in-vivo experiments in humans. Although patterns do emerge from individual studies, there are no clear-cut methods to extrapolate data from one set of compounds to a different series of analogs. However, as has been pointed out above, there are substantial structural, biochemical and functional similarities between skin and oral epithelia, which suggests that it should be possible to identify and quantify trends in oral permeability as a function of the physicochemical properties of the penetrants considered, and to develop predictive relationships similar to those pertaining to skin. We are just now beginning to use the resources of the Computer Graphics Laboratory to locate, examine, and analyze (including, but not limited to, the computation of molecular volumes) peptidic compounds of interest.
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