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SHR Neuro Krebs Kardio Lipid

Bodenlenz, M; Höfferer, C; Magnes, C; Schaller-Ammann, R; Schaupp, L; Feichtner, F; Ratzer, M; Pickl, K; Sinner, F; Wutte, A; Korsatko, S; Köhler, G; Legat, FJ; Benfeldt, EM; Wright, AM; Neddermann, D; Jung, T; Pieber, TR.
Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.
Eur J Pharm Biopharm. 2012; 81(3):635-641
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Autor/innen der Med Uni Graz:
Bodenlenz Manfred
Feichtner Franz
Köhler Gerd
Korsatko Stefan
Legat Franz
Pieber Thomas
Schaupp Lukas
Sinner Frank
Wutte Andrea Maria
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Abstract:
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 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps. 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 h 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. dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1. 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. Copyright © 2012 Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Administration, Cutaneous -
Adult -
Biomarkers - metabolism
Chromatography, Liquid - methods
Enzyme-Linked Immunosorbent Assay -
Equipment Design -
Feasibility Studies -
Female -
Humans -
Male -
Microdialysis - methods
Middle Aged -
Perfusion - methods
Psoriasis - drug therapy
Tandem Mass Spectrometry -
Time Factors -
Tumor Necrosis Factor-alpha - metabolism
Young Adult -
p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors

Find related publications in this database (Keywords)
Open-flow microperfusion
Psoriasis
Topical drugs
Skin penetration
Pharmacokinetics
Pharmacodynamics
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