An exploratory microdialysis study investigating the effect of repeated application of a diclofenac epolamine medicated plaster on prostaglandin concentrations in skeletal muscle after standardized physical exercise

Br J Clin Pharmacol. 2013 Dec;76(6):880-7. doi: 10.1111/bcp.12125.


Aim: Muscle injuries and extensive exercise are associated with cyclo-oxygenase dependent formation of inflammatory prostaglandins. Since the effect of topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) on local cyclo-oxygenase is unknown, the present exploratory, open label, non-randomized study set out to measure exercise induced release of prostaglandins before and after epicutaneous administration of diclofenac.

Methods: Microdialysis was used to determine the local interstitial concentration of PGE2 and 8-iso-PGF2α as well as diclofenac concentrations in the vastus lateralis under rest, dynamic exercise and during recovery in 12 healthy subjects at baseline and after a treatment phase applying a total of seven plasters medicated with 180 mg of diclofenac epolamine over 4 days.

Results: At baseline PGE2 concentrations were 1169 ± 780 pg ml(-1) at rest and 1287 ± 459 pg ml(-1) during dynamic exercise and increased to 2005 ± 1126 pg ml(-1) during recovery. After treatment average PGE2 concentrations were 997 ± 588 pg ml(-1) at rest and 1339 ± 892 pg ml(-1) during exercise. In contrast with the baseline phase no increase in PGE2 concentrations was recorded during the recovery period after treatment (PGE2 1134 ± 874 pg ml(-1)). 8-iso-PGF2α was neither affected by exercise nor by treatment with diclofenac. Local and systemic concentrations of diclofenac were highly variable but comparable with previous clinical pharmacokinetic studies.

Conclusions: We can hypothesize an effect of topical diclofenac epolamine plaster on limiting the increase of local concentrations of the pro-inflammatory prostaglandin PGE2 induced in the muscle of healthy human subjects following standardized physical exercise. No effect of diclofenac treatment on 8-iso-PGF2α concentrations was observed, mainly since isoprostane is produced by a free radical-catalyzed lipid peroxidation mechanism independent of cyclo-oxygenases.

Keywords: diclofenac; microdialsis; pharmacokinetics; transdermal.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal* / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Diclofenac / administration & dosage
  • Diclofenac / analogs & derivatives*
  • Diclofenac / pharmacokinetics
  • Diclofenac / pharmacology
  • Dinoprost / analogs & derivatives*
  • Dinoprost / analysis
  • Dinoprostone / analysis*
  • Dose-Response Relationship, Drug
  • Exercise / physiology*
  • Healthy Volunteers
  • Humans
  • Male
  • Microdialysis
  • Quadriceps Muscle / drug effects*
  • Quadriceps Muscle / metabolism
  • Quadriceps Muscle / physiology
  • Transdermal Patch
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • diclofenac hydroxyethylpyrrolidine
  • Diclofenac
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Dinoprostone