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

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
M BodenlenzT R Pieber

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 lip...Continue Reading

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Citations

Jun 12, 2013·Skin Pharmacology and Physiology·L MelgaardL J Petersen
Mar 14, 2014·PloS One·Thomas BirngruberFrank Sinner
Apr 16, 2013·Skin Research and Technology : Official Journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)·M BodenlenzF Sinner
Jan 1, 2014·Basic & Clinical Pharmacology & Toxicology·Rikke HolmgaardJesper B Nielsen
Jan 8, 2014·Expert Opinion on Pharmacotherapy·Andrea ChiricozziSergio Chimenti
May 20, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Franciska ErdőYukio Kato
Aug 20, 2016·Clinical Pharmacokinetics·Manfred BodenlenzFrank Sinner
Aug 10, 2016·The Journal of Allergy and Clinical Immunology·Frank KolbingerDhavalkumar D Patel
Sep 28, 2016·Journal of Pharmaceutical Sciences·Satyawan B JadhavHartmut Derendorf
Oct 3, 2017·Physiological Measurement·Simon SchwingenschuhMartin Hajnsek
Apr 16, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Xin LiuMichael S Roberts
Jul 13, 2021·Molecular Pharmaceutics·Anne Mette HandlerKim Troensegaard Nielsen

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