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
