title: Microdialysis technique as a method to study the percutaneous penetration of methyl nicotinate through excised human skin, reconstructed epidermis, and human skin in vivo.
abstract: OBJECTIVE
  The aim was to assess the feasibility of cutaneous microdialysis as a method to study percutaneous penetration of methyl nicotinate through human skin in vitro and in vivo.
  
  
  METHODS
  Microdialysis was applied in vitro in excised human skin, in isolated dermis, in reconstructed human epidermis and in vivo in the volar forearm skin of volunteers using methyl nicotinate (MN) as a model compound. After topical application of MN, aliquots of the perfusate were collected and analyzed for the presence of MN spectrophotometrically and by HPLC. In vivo, visual scoring and laser Doppler perfusion imaging (LDPI) were used to monitor the effects on skin blood flow.
  
  
  RESULTS
  In vitro, MN was detected in the dialysate after a 1 min exposure of excised skin to concentrations as low as 25 mM. Higher concentrations up to 500 mM showed increased levels. Prolongation of the application time to 60 min resulted in increased levels of MN in the perfusate as the duration of application increased. Reconstructed epidermis and isolated dermis showed an almost 2- and 20-fold higher penetration compared to excised skin, respectively. In vivo, LDPI measurements showed a rapid increase in skin blood flow after application of 25 to 100 mM MN for 1 min. MN was only detectable in the microdialysate after application of 100 mM for 10 min (two of three subjects).
  
  
  CONCLUSIONS
  Cutaneous microdialysis may be a tool for comparative studies linking responses in human skin in vivo to in vitro data using the same technique and endpoint.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Boelsma
authors.forename: C
authors.initials: C
authors.lastname: Anderson
authors.forename: A M
authors.initials: AM
authors.lastname: Karlsson
authors.forename: M
authors.initials: M
authors.lastname: Ponec
mesh_terms: D000279:Administration, Cutaneous; D002851:Chromatography, High Pressure Liquid; D004817:Epidermis / Q000000981:diagnostic imaging / Q000378:metabolism*; D004890:Erythema / Q000139:chemically induced; D006801:Humans; D066298:In Vitro Techniques; D017078:Laser-Doppler Flowmetry; D017551:Microdialysis / Q000379:methods*; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009539:Nicotinic Acids; C008473:methyl nicotinate