For topical drug products that target sites of action in the viable epidermal and/or upper dermal compartment of the skin,
the local concentration profiles have proven difficult to quantify because drug clearance from the viable cutaneous tissue is
not well characterised. Without such knowledge, of course, it is difficult—if not impossible—to predict a priori whether and
over what time frame a topical formulation will permit an effective concentration of drug within the skin ‘compartment’ to
be achieved. Here, we test the hypothesis that valuable information about drug disposition, and specifically its clearance, in
this experimentally difficult-to-access compartment (at least, in vivo) can be derived from available systemic pharmacokinetic
data for drugs administered via transdermal delivery systems. A multiple regression analysis was undertaken to determine the
best-fit empirical correlation relating clearance from the skin to known or easily calculable drug properties. It was possible,
in this way, to demonstrate a clear relationship between drug clearance from the skin and key physical chemical properties
of the drug (molecular weight, log P and topological polar surface area). It was further demonstrated that values predicted
by the model correlated well with those derived from in vitro skin experiments.
Original languageEnglish
Pages (from-to)729–740
Number of pages12
JournalDrug Delivery and Translational Research
Early online date8 Nov 2020
Publication statusPublished - 30 Apr 2021


Dive into the research topics of 'Predicting topical drug clearance from the skin'. Together they form a unique fingerprint.

Cite this