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. (December 2013)

• Record Type: Journal Article
• Authors: Burian, Angela; Frangione, Valeria; Rovati, Stefano; Mautone, Giuseppe; Leuratti, Chiara; Vaccani, Angelo; Crevenna, Richard; Keilani, Mohammad; Burian, Bernhard; Brunner, Martin; Zeitlinger, Markus
• Is Part Of: British journal of clinical pharmacology. Volume 76:Number 6(2013:Dec.)
• Page Start: 880
• Page End: 887
• Publication Date: 2013-12
• Subjects: Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.12125
• Languages: English
• ISSNs: 0306-5251

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bcp12125-sec-0001" sec-type="section"> <title>Aim</title> <p>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.</p> </sec> <sec id="bcp12125-sec-0002" sec-type="section"> <title>Methods</title> <p>Microdialysis was used to determine the local interstitial concentration of PGE<sub>2</sub> and 8‐iso‐PGF<sub>2α</sub> 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.</p> </sec> <sec id="bcp12125-sec-0003" sec-type="section"> <title>Results</title> <p>At baseline PGE<sub>2</sub> concentrations were 1169 ± 780 pg ml<sup>−1</sup> at rest and 1287 ± 459 pg ml<sup>−1</sup> during dynamic exercise and increased to 2005 ± 1126 pg ml<sup>−1</sup> during recovery. After treatment average PGE<sub>2</sub> concentrations were 997 ± 588 pg ml<sup>−1</sup> at rest and 1339 ± 892 pg ml<sup>−1</sup> during exercise. In contrast with the baseline phase no increase in PGE<sub>2</sub> concentrations was recorded during the recovery period after treatment (PGE<sub>2</sub> 1134 ± 874 pg ml<sup>−1</sup>). 8‐iso‐PGF<sub>2α</sub> 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.</p> </sec> <sec id="bcp12125-sec-0004" sec-type="section"> <title>Conclusions</title> <p>We can hypothesize an effect of topical diclofenac epolamine plaster on limiting the increase of local concentrations of the pro‐inflammatory prostaglandin PGE<sub>2</sub> induced in the muscle of healthy human subjects following standardized physical exercise. No effect of diclofenac treatment on 8‐iso‐PGF<sub>2α</sub> concentrations was observed, mainly since isoprostane is produced by a free radical‐catalyzed lipid peroxidation mechanism independent of cyclo‐oxygenases.</p> </sec> </abstract>