{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:45:01Z","timestamp":1791654301766,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>There is a potential risk of systemic side\u2010effects 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\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 12 clinical studies in healthy\u00a0adult 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%\u201360% of body surface area [BSA]) on systemic exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The PBPK model described the absorption and disposition characteristics of CP. Mean clearance, volume of distribution (V\n                      <jats:sub>ss<\/jats:sub>\n                      ) and renal clearance were 27\u2009L\/h, 2.34\u2009L\/kg and 0.12\u2009L\/h, respectively. The half\u2010life of CP after topical application was significantly longer than after an IV dose (20.8\n                      <jats:italic>vs<\/jats:italic>\n                      . 5.2\u2009h). 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Systemic and local exposure to CP increases with impaired skin barrier in AD and larger application area. Given the recommended maximum dose of 50\u2009g 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70102","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T07:45:03Z","timestamp":1752219903000},"page":"3150-3166","source":"Crossref","is-referenced-by-count":9,"title":["Characterizing local and systemic exposure to clobetasol propionate in healthy subjects and patients with atopic dermatitis"],"prefix":"10.1002","volume":"91","author":[{"given":"Janna K.","family":"Duong","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Modelling &amp; Simulation GSK  Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"van Dijkman","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modelling &amp; Simulation GSK  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Ong","sequence":"additional","affiliation":[{"name":"Pharma Research and Development Global Medical, GSK  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Marta","sequence":"additional","affiliation":[{"name":"Pharma Research and Development Global Medical, GSK  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Ceci","sequence":"additional","affiliation":[{"name":"Pharmacological Research Foundation \u2018Gianni Benzi\u2019  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Bonifazi","sequence":"additional","affiliation":[{"name":"Past professor of Pediatric Dermatology \u201cAldo Moro\u201d University Bari  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-1430","authenticated-orcid":false,"given":"Oscar","family":"Della Pasqua","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Modelling &amp; Simulation GSK  UK"},{"name":"Clinical Pharmacology &amp; Therapeutics Group University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"GlaxoSmithKline.2024.Dermovate cream SmPC. 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