title: Pharmacokinetic profile of methotrexate in psoriatic skin via the oral or subcutaneous route using dermal microdialysis showing higher methotrexate bioavailability in psoriasis plaques than in non-lesional skin.
abstract: OBJECTIVE
  The aim of this pilot study was to use microdialysis to evaluate levels of Methotrexate (MTX) directly in psoriatic skin following oral or subcutaneous administration of MTX to elaborate a complete pharmacokinetic profile within the dermal skin.
  
  
  METHODS
  Six patients with chronic plaque psoriasis on the arm undergoing treatment with MTX were included in a mono-centre clinical trial. Patients were under treatment with p.o. or s.c. MTX (7.5 and 15 mg) for at least 3 months. Interstitial fluid was collected ex vivo via dermal microdialysis from lesional or non-lesional skin and via intravenous microdialysis as well as blood serum every hour up to 10 h after methotrexate administration every hour. MTX was analysed via liquid chromatography.
  
  
  RESULTS
  The area under the curve (AUC) of methotrexate from peripheral blood was up to four times higher than from microdiaylsis, which detection of free unbound MTX. The AUC from dialysates in psoriatic lesional skin was higher than in non-lesional psoriatic skin, and the AUC levels from i.v. microdialysis were non-significantly higher than those from lesional psoriatic skin. Pharmacokinetic profiles were individually quite different and did not primarily depend on the dose or the means (p.o. vs. s.c.) in which it was administered.
  
  
  CONCLUSIONS
  Dermal microdialysis is a valid tool to evaluate levels of methotrexate in the skin of psoriasis patients. Drug levels and bioavailability of methotrexate were higher in lesional than non-lesional psoriatic skin. The individual AUC of MTX was not primarily dependent on the route or dose of administration.
authors.affiliation: Clinic of Dermatology and Venereology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Quist
authors.affiliation: Clinic of Dermatology and Venereology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Quist
authors.affiliation: Laboratory Volkmann, Central Medical Laboratory, Karlsruhe, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Birkenmaier
authors.affiliation: Laboratory Volkmann, Central Medical Laboratory, Karlsruhe, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Stauch
authors.affiliation: Clinic of Dermatology and Venereology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Gollnick
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001682:Biological Availability; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017551:Microdialysis; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D003879:Dermatologic Agents; D008727:Methotrexate