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Abstract
1. The delivery of drugs via the skin to achieve systemic therapeutic effect is currently under intense investigation.
2. The skin offers unique advantages and limitations for drug input into the body. For example, while hepatic first pass may be circumvented, the excellent barrier function of the stratum corneum (the thin outermost layer of skin) precludes, at present, all but the most potent drugs from this route of administration.
3. Examples of approved transdermally delivered drugs are scopolamine, nitroglycerin, clonidine and estradiol. The delivery systems which have been formulated for these agents have been designed to provide essentially zero-order input kinetics for between 1 and 7 days.
4. The impact of cutaneous metabolism on transdermal drug delivery has not yet been evaluated rigorously. Limited in vivo data for nitroglycerin suggest a cutaneous first pass effect of between 10 and 20%.
5. More work has been directed towards the use of topical prodrugs and the design of molecules better able to transport across the stratum corneum and then undergo local enzymatic activation.
6. Further research in this area will require a more specific quantitative understanding of the metabolic capabilities of human skin in vivo.