Duon, Janna K;
Van Dijkman, Sven;
Ong, Gary;
Marta, Alexandra;
Ceci, Adriana;
Bonifazi, Ernesto;
Della Pasqua, Oscar;
(2025)
Characterizing local and systemic exposure to clobetasol propionate in healthy subjects and patients with atopic dermatitis.
British Journal of Clinical Pharmacology
10.1002/bcp.70102.
(In press).
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Abstract
Aims: There is a potential risk of systemic side-effects with the use of potent corticosteroids, such as clobetasol propionate (CP). This concern is of particular interest in paediatric patients. The aim of this study was to develop and verify a physiologically based pharmacokinetic (PBPK) model to describe the local and systemic exposure to CP following topical application over a period of up to 4 weeks. Methods: Data from 12 clinical studies in healthy adult subjects and patients with atopic dermatitis (AD) were available for this investigation. A PBPK model including skin barrier impairment was developed to predict the effect of AD lesions on systemic exposure. Simulation scenarios were then evaluated to assess the effect of formulation, skin condition and surface area (5%–60% of body surface area [BSA]) on systemic exposure. Results: The PBPK model described the absorption and disposition characteristics of CP. Mean clearance, volume of distribution (Vss) and renal clearance were 27 L/h, 2.34 L/kg and 0.12 L/h, respectively. The half-life of CP after topical application was significantly longer than after an IV dose (20.8 vs. 5.2 h). Systemic CP concentrations were higher with increasing surface area and skin barrier impairment. However, CP accumulates in the stratum corneum as the skin barrier function improves during treatment. Conclusions: Systemic and local exposure to CP increases with impaired skin barrier in AD and larger application area. Given the recommended maximum dose of 50 g per week, CP should not be applied to an area of more than 30% of the BSA. Availability of this model will allow extrapolation of CP pharmacokinetics from adults to children.
| Type: | Article |
|---|---|
| Title: | Characterizing local and systemic exposure to clobetasol propionate in healthy subjects and patients with atopic dermatitis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/bcp.70102 |
| Publisher version: | https://doi.org/10.1002/bcp.70102 |
| Language: | English |
| Additional information: | © 2025 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | atopic dermatitis, clobetasol propionate, corticosteroids, PBPK modelling, systemic exposure, tissue exposure |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10208223 |
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