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Comparison of In Vitro and In Vivo Percutaneous Absorption Across Human Skin Using BAY1003803 Formulated as Ointment and Cream
Author(s) -
Günther Clemens,
Kowal Kristin,
Schmidt Timm,
Jambrecina Alen,
Toner Frank,
Nave Rüdiger
Publication year - 2020
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.736
Subject(s) - in vivo , human skin , permeation , medicine , in vitro , pharmacology , pharmacokinetics , absorption (acoustics) , bioavailability , dermatology , chromatography , biomedical engineering , chemistry , materials science , biochemistry , biology , microbiology and biotechnology , genetics , composite material , membrane
Abstract Direct comparisons between skin absorption data and clinical pharmacokinetic data are rare. Here we use the lipophilic nonsteroidal selective glucocorticoid receptor agonist BAY1003803 to make such a comparison. The objective is to find the extent to which measurements of skin permeation in vitro can be used to predict the corresponding permeation in vivo for human pharmacokinetics of topically applied substances. BAY1003803 was prepared in various formulations: ointment, hydrophilic cream, lipophilic cream, and milk. Its ability to permeate healthy human skin was measured in vitro in static diffusion cells, and percutaneous absorption as well as dermal delivery was measured thereafter, for 2 selected formulations, in vivo in healthy volunteers. Absorption in vivo comparing ointment and lipophilic cream was correlated with expectation based on the dermal delivery obtained in vitro. A 2.17‐fold higher systemic exposure to BAY1003803 was achieved by the ointment formulation. This is well in line with the predicted exposure difference of 2.74 based on the in vitro data. In conclusion, in vitro skin absorption studies using human skin are suitable for the prediction of systemic exposure and formulation effects in vivo; they can therefore be applied to guide the design of clinical investigations of dermatological preparations.