کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2083958 | 1545359 | 2012 | 7 صفحه PDF | دانلود رایگان |
BackgroundMethodologies 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 25 h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.MethodsNine 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.ResultsdOFM 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.ConclusionsNovel 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.
Access to the dermis for continuous PK/PD sampling is provided by a new, minimally invasive, membrane-free method: dermal open-flow microperfusion (dOFM). PK profiles and AUC 24h indicate accumulation of BCT194 in the dermis of both psoriatic lesional skin and non-lesional skin.Figure optionsDownload high-quality image (236 K)Download as PowerPoint slide
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 81, Issue 3, August 2012, Pages 635–641