title: Clarifications: Dermal Clearance Model for Epidermal Bioavailability Calculations.
abstract: Delivery through the skin, either through topical application for therapeutic or cosmetic benefits or intradermal delivery through emerging technologies such as microneedles, has been studied extensively in past decades. In a previous report in this journal one of the authors proposed an extensive model for predicting dermal clearance under pseudo steady-state conditions from the physiochemical properties of the compound (Ibrahim et al. 2012 J Pharm Sci, 101:2094-2108). This note provides some clarifications regarding this model, highlighting critical points that must be considered when using the model. The points are discussed in the order of relevance and complement the understanding of how molecules delivered intradermally clear from the dermis into the systemic circulation. In brief, solute binding to protein is reconsidered, limitations in using empirical models to determine physiochemical properties of a molecule are highlighted, and readers are informed about critical details regarding the calculations.
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033. Electronic address: yash.kapoor@merck.com.
authors.forename: Yash
authors.initials: Y
authors.lastname: Kapoor
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors.forename: Mikolaj
authors.initials: M
authors.lastname: Milewski
authors.affiliation: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors.forename: Amitava
authors.initials: A
authors.lastname: Mitra
authors.affiliation: James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, Ohio 45267. Electronic address: kastingb@ucmail.uc.edu.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Kasting
mesh_terms: D001682:Biological Availability; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D012867:Skin / Q000378:metabolism*
keywords: absorption; lymphatic transport; mathematical model; physiologically based pharmacokinetic modeling; protein binding; transdermal