title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Burian
authors.forename: Valeria
authors.initials: V
authors.lastname: Frangione
authors.forename: Stefano
authors.initials: S
authors.lastname: Rovati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mautone
authors.forename: Chiara
authors.initials: C
authors.lastname: Leuratti
authors.forename: Angelo
authors.initials: A
authors.lastname: Vaccani
authors.forename: Richard
authors.initials: R
authors.lastname: Crevenna
authors.forename: Mohammad
authors.initials: M
authors.lastname: Keilani
authors.forename: Bernhard
authors.initials: B
authors.lastname: Burian
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis; D015232:Dinoprostone / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D015444:Exercise / Q000502:physiology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D017551:Microdialysis; D052097:Quadriceps Muscle / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C064142:diclofenac hydroxyethylpyrrolidine; D004008:Diclofenac; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D015232:Dinoprostone
keywords: diclofenac; microdialsis; pharmacokinetics; transdermal
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