Regional Variations in Percutaneous Absorption

October 2012 | Volume 11 | Issue 10 | Original Article | e48 | Copyright © 2012

Abstract

Background: In its simplest definition, percutaneous absorption (PA) is the amount of substance that passes through the stratum corneum compared with the amount applied. The study of the PA of substances is relevant to the fields of dermatopharmacology and occupational medicine. The quantity and rate in which a given chemical absorbs through the skin depend on a multitude of variables. One obvious determinant of PA is the application site. This overview summarizes currently available data on the topic of regional variations in PA and possibly suggests a direction for future research efforts.
Methods: Searches were performed in Medline and EMBASE. Extensive bibliographical research was performed in order to identify additional relevant data sets using Web of Science. Results were screened for inclusion of more than one anatomical site, the use of validated methods, and the use of human subjects.
Results: We identified eight relevant studies, from which we present data.
Conclusion: Determining regional variations in PA is a complex yet critically important task. Current data sets are scarce and inadequate for drawing complete conclusions, but the data seem to suggest increased PA in the forehead and genital skin compared with other anatomical regions. It is our hope that, with the advent of new technologies, an anatomical PA map will begin to emerge from the data. Such descriptive understanding will guide investigation into the mechanisms involved in determining anatomical site differences in PA.

J Drugs Dermatol. 2012;11(10):e48-e51.

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INTRODUCTION

The study of percutaneous absorption (PA) of substances is relevant to the fields of dermatopharmacology (such as in the cases of drug delivery methods and chemical warfare) and occupational medicine (such as in the case of pesticides). In its simplest definition, PA is the amount of substance that passes through the stratum corneum compared with the amount applied. The quantity of any given chemical that absorbs through the skin, as well as the rate of absorption, depends on the dose (ie, the amount applied, the concentration of the active substance in the formulation, and the area and duration of application), the vehicle, and the chemical properties of the substance (molecular size, solubility, charge, and pH). In addition, external factors such as humidity, occlusion, and pathology can modify penetration. Finally, the physical and functional properties of the epidermis and, specifically, the stratum corneum at any given location will alter absorption properties.1-4

One obvious determinant of PA is the application site. This particular aspect in the study of PA dates at least as far back in the literature as 1947.5 Feldmann and Maibach's seminal studies in the late 1960s and 1970s have set the modern framework for our current understanding of the topic.6 However, and not for lack of trying, there is still a gap in our understanding of the processes that govern regional variations in PA, which most likely stems from the sheer complexity of the topic. Therefore, an intelligent model for explaining the absorption differences noted with respect to anatomical site variation is needed. This need is becoming increasingly critical in order to keep up with pharmacological advances that offer, for instance, more and more medications via dermal slow-release preparations. This overview summarizes currently available data on the topic of regional variations in PA and suggests a possible direction for future research efforts.

METHODS

Various methods have been employed in the evaluation of PA. These can be divided into in vivo and in vitro (including ex vivo) methods. This overview focuses on human in vivo studies only. Transepidermal water loss (TEWL), laser Doppler flowmetry (LDF), tape stripping, and urinary measurements of radioactive-labeled carbon are the most common in vivo methods documented in the study of PA. However, evidence for the validity of TEWL in predicting proclivity to PA is complex, and while the weight of the evidence suggests that a relationship does exist between TEWL and PA, the nature of this relationship is unclear and, therefore, inappropriate for use in this overview.7,8 LDF is another surrogate measurement and is potentially subject to many biases, one of which is blood flow variations between various anatomical sites, and so it is also inappropriate for the purpose of this essay.

The tape-stripping method involves applying a compound of choice for 30 minutes and then measuring the amount of the material in the layers of the stratum corneum. Stratum corneum

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