Purpose: Percutaneous penetration in man is affected by several factors: chemical properties, skin anatomy variables, and environmental conditions can all modify the quantity of chemical that penetrates through the skin barrier. The amount of chemical or drug that penetrates the cutaneous barrier must be considered due to the local and systemic absorption that may occur. Regional variation in percutaneous absorption is an additional factor to recognize when analysing chemical percutaneous penetration. Although it has been studied that certain anatomic sites allow for increased absorption, there is limited literature regarding in vivo data in man. This overview catalogues and analyses studies performed in man to quantify chemical permeation at varying anatomical locations. We also review what is known about the pharmacokinetics of Food and Drug Administration approved medication patches and semisolids and the regional variation in absorption that they may display. This research work aims to create an updated, concise overview of the pertinent studies available regarding percutaneous penetration and regional variability.
Materials and methods: We searched PubMed, Web of Science, Google Scholar and the United States Food and Drug Administration's online database for approved transdermal delivery systems from January 1965 to March 2020, with the search words: percutaneous absorption, regional variation, anatomical location, along with extensive bibliographical review. We further utilized the prior listed search engines to search for published data pertaining to regional differences in percutaneous absorption for each of the FDA-approved medications. If no publication was found, we utilized the Summary Basis of Approval documents for each medication to determine patch application site pharmacokinetics.
Results: Several chemical containing gels and solutions were tested for regional variability. Chemical characteristics and body site location were determinants in absorption. In general, the head, neck and genitalia contamination resulted in greatest absorption, whereas trunk, back, and thighs resulted in less absorption. Most of the FDA-approved transdermal delivery patch medications are efficacious at more than one body location, allowing for greater patient convenience when choosing patch location.
Conclusions: Regional variability in chemical and drug absorption is of clinical and pharmacological significance. More studies determining in vivo percutaneous absorption in man are necessary to further understand the role of regional variation, the mechanisms involved, and how to derive reliable formulas for extrapolating flux from one anatomic site to the next, often required for risk assessments.
Keywords: Percutaneous absorption; anatomical location; regional variation.