title: Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling.
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 25h 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 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.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., Graz, Austria.
authors.forename: Manfred
authors.initials: M
authors.lastname: Bodenlenz
authors.forename: Christian
authors.initials: C
authors.lastname: Höfferer
authors.forename: Christoph
authors.initials: C
authors.lastname: Magnes
authors.forename: Roland
authors.initials: R
authors.lastname: Schaller-Ammann
authors.forename: Lukas
authors.initials: L
authors.lastname: Schaupp
authors.forename: Franz
authors.initials: F
authors.lastname: Feichtner
authors.forename: Maria
authors.initials: M
authors.lastname: Ratzer
authors.forename: Karin
authors.initials: K
authors.lastname: Pickl
authors.forename: Frank
authors.initials: F
authors.lastname: Sinner
authors.forename: Andrea
authors.initials: A
authors.lastname: Wutte
authors.forename: Stefan
authors.initials: S
authors.lastname: Korsatko
authors.forename: Gerd
authors.initials: G
authors.lastname: Köhler
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Legat
authors.forename: Eva M
authors.initials: EM
authors.lastname: Benfeldt
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Wright
authors.forename: Daniel
authors.initials: D
authors.lastname: Neddermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Jung
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pieber
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D004867:Equipment Design; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods*; D008875:Middle Aged; D010477:Perfusion / Q000379:methods; D011565:Psoriasis / Q000188:drug therapy*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases