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

作者：Burian Angela; Frangione Valeria; Rovati Stefano; Mautone Giuseppe; Leuratti Chiara; Vaccani Angelo; Crevenna Richard; Keilani Mohammad; Burian Bernhard; Brunner Martin; Zeitlinger Markus^*

来源：British Journal of Clinical Pharmacology, 2013, 76(6): 880-887.

DOI：10.1111/bcp.12125

• diclofenac
• microdialsis
• pharmacokinetics
• transdermal

AIM %26lt;br%26gt;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. %26lt;br%26gt;METHODS %26lt;br%26gt;Microdialysis was used to determine the local interstitial concentration of PGE(2) and 8-iso-PGF(2 alpha) 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. %26lt;br%26gt;RESULTS %26lt;br%26gt;At baseline PGE(2) 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 PGE(2) 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 PGE(2) concentrations was recorded during the recovery period after treatment (PGE(2) 1134 +/- 874 pg ml(-1)). 8-iso-PGF(2 alpha) 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. %26lt;br%26gt;CONCLUSIONS %26lt;br%26gt;We can hypothesize an effect of topical diclofenac epolamine plaster on limiting the increase of local concentrations of the pro-inflammatory prostaglandin PGE(2) induced in the muscle of healthy human subjects following standardized physical exercise. No effect of diclofenac treatment on 8-iso-PGF(2 alpha) concentrations was observed, mainly since isoprostane is produced by a free radical-catalyzed lipid peroxidation mechanism independent of cyclo-oxygenases.

• 出版日期2013-12