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Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

Bodenlenz, Manfred and Höfferer, Christian and Magnes, Christoph and Schaller, R. and Schaupp, L. and Feichtner, F. and Ratzer, Maria and Pickl, Karin and Sinner, Frank and Wutte, A. and Korsatko, S. and Köhler, G. and Legat, F.J. and Benfeldt, E. and Wright, Andrew and Neddermann, Daniel and Jung, Thomas and Pieber, Thomas R. (2012) Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling. European Journal of Pharmaceutics and Biopharmaceutics, 81 (3). pp. 635-641. ISSN 0939-6411

Abstract

Background: Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25hrs by means of membrane-free dermal Open-Flow Microperfusion probes (dOFM) and novel wearable multi-channel pumps.
Methods: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 hours from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight Push-Pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis.
Results: dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after eight days but did not show significant differences between tissues. On day 8 TNFα release following probe insertion was significantly reduced compared to day 1.
Conclusions: Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting.

Item Type: Article
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Additional Information: A paid open access option is available for this journal.
Keywords: Open Flow Microperfusion, Psoriasis, topical, Skin penetration, pharmacokinetics, pharmacodynamics
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/7311

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