Elucidating Fundamental Principles of Dermal Pharmacokinetics via Microdialysis

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PROJECT SUMMARY: This project responds to Funding Opportunity RFA-FD-20-019, “Bioequivalence of Topical Products: Elucidating Fundamental Principles of Dermal Pharmacokinetics for Microdialysis or Microperfusion Techniques (U01)”. The purpose of this proposal is to elucidate how pharmacokinetic principles and concepts (e.g., dose, fraction of drug absorbed, apparent volume of distribution, Cmax, AUCinfinity) should be applied or adapted when evaluating the rate and extent to which a topically applied compound becomes available in the dermis, at or near a site of action within the skin. The proposed work uses in vivo microdialysis to characterize dermis pharmacokinetics following the administration of drugs (i) directly in dermis via a retrodialysis/microdialysis approach (dermal infusion), and (ii) topically, from dermatological formulations. The results of these studies will permit a thorough characterization of dermis permeability (absorption), distribution, metabolism, and elimination (ADME), which will elucidate whether or not the fundamental assumptions that underlie bioequivalence assessment for systemic formulations can be applied to topical formulations. In addition, characterization of dermal ADME processes can be used to develop new strategies, concepts, and endpoints to address the issue of bioequivalence of topical dermatological drug products.