At least 20 clinically relevant factors affect percutaneous absorption of drugs and chemicals: relevant physico-chemical properties, vehicle/formulation, drug exposure conditions (dose, duration, surface area, exposure frequency), skin appendages (hair follicles, glands) as sub-anatomical pathways, skin application sites (regional variation in penetration), population variability (premature, infants, and aged), skin surface conditions (hydration, temperature, pH), skin health and integrity (trauma, skin diseases), substantivity and binding to different skin components, systemic distribution and systemic toxicity, stratum corneum exfoliation, washing-off and washing-in, rubbing/massaging, transfer to others (human to human and hard surface to human), volatility, metabolic biotransformation/cutaneous metabolism, photochemical transformation and photosensitivity, excretion pharmacokinetics, lateral spread, and chemical method of determining percutaneous absorption.
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RML had the idea to provide a practical and clinically relevant version of MAN and HIM pivotal paper on 15 steps of percutaneous absorption—for practitioners—and in the process expanded the discussion to 20 factors, with contribution from HIM; RML performed the literature search, with additional sources from HIM vast experience; RML drafted the work; HIM critically revised the work at multiple timepoints, RML critically revised the work several times, and MAN critically revised the work twice.
Compliance with Ethical Standards
There were no sources of funding for this review.
Conflict of interest
Rebecca M. Law, Mai A. Ngo, and Howard I. Maibach have no conflicts of interest relating to this review.
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