Chirality in Drug Design and Development第3章.pdf

3 Transport of Chiral Molecules Across the Skin Elka Touitou and Biana Godin The Hebrew University of Jerusalem, Jerusalem, Israel Thirumala R. Kommuru Pfizer Global Research and Development, Ann Arbor, Michigan, U.S.A. Mohsen I. Afouna University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. Indra K. Reddy Texas AM University School of Pharmacy, Kingsville, Texas, U.S.A. 1. INTRODUCTION In the last decade, a number of investigations describing the percutaneous permeation of different stereoforms of chiral compounds have been reported. The rational development of products for transdermal drug delivery requires a thorough understanding of both the biological composition of the skin barrier and the physicochemical properties of drug molecules. For chiral drugs with the biological activity associated with one enantiomer, enantioselective permeation would affect the pharmaco- dynamic profile of the racemate. In such cases, development of a trans- dermal delivery system based on a single enantiomer, rather than racemate, could reduce the optimal therapeutic dose required to achieve the desired pharmacological effect, which in turn can minimize or eliminate the adverse effects associated