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Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution
PURPOSE: To evaluate the kinetics of topically applied clobetasol-17-propionate (CP-17) in lesional and non-lesional psoriatic skin when released from a commercially available low-strength cream using in vivo dermal open-flow microperfusion (dOFM). METHODS: Twelve patients received Dermovate® cream...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967091/ https://www.ncbi.nlm.nih.gov/pubmed/27271272 http://dx.doi.org/10.1007/s11095-016-1960-y |
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author | Bodenlenz, Manfred Dragatin, Christian Liebenberger, Lisa Tschapeller, Bernd Boulgaropoulos, Beate Augustin, Thomas Raml, Reingard Gatschelhofer, Christina Wagner, Nathalie Benkali, Khaled Rony, Francois Pieber, Thomas Sinner, Frank |
author_facet | Bodenlenz, Manfred Dragatin, Christian Liebenberger, Lisa Tschapeller, Bernd Boulgaropoulos, Beate Augustin, Thomas Raml, Reingard Gatschelhofer, Christina Wagner, Nathalie Benkali, Khaled Rony, Francois Pieber, Thomas Sinner, Frank |
author_sort | Bodenlenz, Manfred |
collection | PubMed |
description | PURPOSE: To evaluate the kinetics of topically applied clobetasol-17-propionate (CP-17) in lesional and non-lesional psoriatic skin when released from a commercially available low-strength cream using in vivo dermal open-flow microperfusion (dOFM). METHODS: Twelve patients received Dermovate® cream (CP-17, 0.05%) on small lesional and non-lesional skin test sites for 14 days, once daily. On day 1 and 14, dOFM samples were continuously taken in the dermis for 24 h post-dose and analyzed by LC-MS/MS. Probe depths were assessed by 50 MHz ultrasound scanning. RESULTS: Mixed-effects modelling identified skin condition, treatment duration and probe-depth as kinetics determining variables. The time- and depth-resolved intradermal data revealed (i) slower penetration of CP-17 into lesional than into non-lesional skin, (ii) normalized (faster) skin penetration after repeated dosing, and (iii) no CP-17 accumulation within the dermis independently of the skin condition. CONCLUSIONS: Intradermal investigation of a highly lipophilic drug released from low-strength cream was successfully performed by using dOFM and timely and spatially, i.e., probe-depth dependent, resolved kinetic data were delivered. These data support the assumption that the thickened psoriatic stratum corneum might act as trap compartment which lowers the skin penetration rate for lipophilic topical drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11095-016-1960-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4967091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-49670912016-08-11 Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution Bodenlenz, Manfred Dragatin, Christian Liebenberger, Lisa Tschapeller, Bernd Boulgaropoulos, Beate Augustin, Thomas Raml, Reingard Gatschelhofer, Christina Wagner, Nathalie Benkali, Khaled Rony, Francois Pieber, Thomas Sinner, Frank Pharm Res Research Paper PURPOSE: To evaluate the kinetics of topically applied clobetasol-17-propionate (CP-17) in lesional and non-lesional psoriatic skin when released from a commercially available low-strength cream using in vivo dermal open-flow microperfusion (dOFM). METHODS: Twelve patients received Dermovate® cream (CP-17, 0.05%) on small lesional and non-lesional skin test sites for 14 days, once daily. On day 1 and 14, dOFM samples were continuously taken in the dermis for 24 h post-dose and analyzed by LC-MS/MS. Probe depths were assessed by 50 MHz ultrasound scanning. RESULTS: Mixed-effects modelling identified skin condition, treatment duration and probe-depth as kinetics determining variables. The time- and depth-resolved intradermal data revealed (i) slower penetration of CP-17 into lesional than into non-lesional skin, (ii) normalized (faster) skin penetration after repeated dosing, and (iii) no CP-17 accumulation within the dermis independently of the skin condition. CONCLUSIONS: Intradermal investigation of a highly lipophilic drug released from low-strength cream was successfully performed by using dOFM and timely and spatially, i.e., probe-depth dependent, resolved kinetic data were delivered. These data support the assumption that the thickened psoriatic stratum corneum might act as trap compartment which lowers the skin penetration rate for lipophilic topical drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11095-016-1960-y) contains supplementary material, which is available to authorized users. Springer US 2016-06-06 2016 /pmc/articles/PMC4967091/ /pubmed/27271272 http://dx.doi.org/10.1007/s11095-016-1960-y Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Paper Bodenlenz, Manfred Dragatin, Christian Liebenberger, Lisa Tschapeller, Bernd Boulgaropoulos, Beate Augustin, Thomas Raml, Reingard Gatschelhofer, Christina Wagner, Nathalie Benkali, Khaled Rony, Francois Pieber, Thomas Sinner, Frank Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution |
title | Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution |
title_full | Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution |
title_fullStr | Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution |
title_full_unstemmed | Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution |
title_short | Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution |
title_sort | kinetics of clobetasol-17-propionate in psoriatic lesional and non-lesional skin assessed by dermal open flow microperfusion with time and space resolution |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967091/ https://www.ncbi.nlm.nih.gov/pubmed/27271272 http://dx.doi.org/10.1007/s11095-016-1960-y |
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