Comparison of In Vitro and In Vivo Percutaneous Absorption Across Human Skin Using BAY1003803 Formulated as Ointment...

Area of Science:

• Pharmacology
• Dermatology
• Drug Delivery

Background:

• Direct comparisons between in vitro skin absorption and in vivo clinical pharmacokinetic data are scarce.
• Selective glucocorticoid receptor agonists are used in topical formulations.
• BAY1003803 is a lipophilic nonsteroidal selective glucocorticoid receptor agonist.

Purpose of the Study:

• To assess the predictability of in vitro skin permeation measurements for in vivo human pharmacokinetics of topically applied drugs.
• To compare the in vivo percutaneous absorption and dermal delivery of different formulations of BAY1003803.
• To establish the utility of in vitro skin absorption studies in guiding the design of clinical investigations for dermatological preparations.

Main Methods:

• BAY1003803 was formulated into ointment, hydrophilic cream, lipophilic cream, and milk.
• In vitro skin permeation was measured using static diffusion cells with healthy human skin.
• In vivo percutaneous absorption and dermal delivery were assessed in healthy volunteers for two selected formulations.

Main Results:

• In vitro dermal delivery correlated with in vivo absorption for ointment and lipophilic cream formulations.
• The ointment formulation resulted in a 2.17-fold higher systemic exposure compared to the lipophilic cream.
• The observed in vivo exposure difference closely matched the 2.74-fold difference predicted by in vitro data.

Conclusions:

• In vitro skin absorption studies using human skin effectively predict in vivo systemic exposure.
• In vitro data can reliably forecast the impact of formulation on drug absorption.
• These findings support the use of in vitro skin absorption studies to optimize the development of topical dermatological preparations.