title: In vivo determination of the diclofenac skin reservoir: comparison between passive, occlusive, and iontophoretic application.
abstract: OBJECTIVE
  There is scarce information concerning the pharmacodynamic behavior of topical substances used in the physiotherapy setting. The aim of the present study was to estimate the formation and emptying of the diclofenac (DF) skin reservoir after passive, semiocclusive, and electrically assisted applications of DF.
  
  
  METHODS
  Five different groups of healthy volunteers (ntotal=60, 23 male and 37 female), participated in this study. A 1% DF (Voltaren Emulgel) formulation (12 mg) was applied on the volar forearms on randomized defined circular skin areas of 7 cm(2). DF was applied for 20 minutes under three different conditions at the same time. The presence of DF in the skin results in a reduction of the methyl nicotinate (MN) response. To estimate the bioavailability of DF in the skin, MN responses at different times following initial DF application (1.5, 6, 24, 32, 48, 72, 96, and 120 hours) were analyzed.
  
  
  RESULTS
  At 1.5 hours after the initial DF application, a significant decrease in MN response was detected for the occluded and iontophoretic delivery. Passive application resulted in a decrease of the MN response from 6 hours post-DF application. The inhibition remained up to 32 hours post-DF application for the iontophoretic delivery, 48 hours for the occluded application, and 72 hours for the passive delivery. At 96 and 120 hours post-DF application none of the MN responses was inhibited.
  
  
  CONCLUSIONS
  The formation and emptying of a DF skin reservoir was found to be dependent on the DF-application mode. Penetration-enhanced delivery resulted in a faster emptying of the reservoir.
authors.affiliation: Department of Health Sciences, University of Applied Sciences and Arts of Southern Switzerland, Landquart, Switzerland ; Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Ron
authors.initials: R
authors.lastname: Clijsen
authors.affiliation: Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Baeyens
authors.affiliation: Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: André Odilon
authors.initials: AO
authors.lastname: Barel
authors.affiliation: Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Clarys
mesh_terms: D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007478:Iontophoresis; D008297:Male; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac
keywords: diclofenac; iontophoresis; occlusion; passive diffusion; transdermal drug delivery