title: Comparison of the efficacy and skin permeability of topical NSAID preparations used in Europe.
abstract: This study compared the efficacy and skin permeability of nine topical preparations of nonsteroidal anti-inflammatory drugs (NSAIDs) (ketoprofen, diclofenac, flurbiprofen, and piroxicam patches; and ketoprofen, diclofenac, piroxicam, niflumic acid, and ibuprofen gels) available in the European Union. The anti-inflammatory effect of these NSAID preparations was evaluated in rat models of acute inflammation (carrageenan or yeast treatment) and chronic inflammation (collagen or adjuvant treatment). Skin permeability of the preparations was evaluated in vitro using mouse skin. In rats with acute inflammation, both ketoprofen preparations significantly inhibited carrageenan-induced edema and yeast-induced hyperalgesia. Flurbiprofen and diclofenac preparations also showed a significant anti-inflammatory effect, but the ketoprofen products were the most potent among the four patch preparations and five gel preparations. With repeated application, the ketoprofen patch significantly decreased edema from day 3 in collagen-treated rats, while other preparations (ketoprofen gel, diclofenac patch, and diclofenac gel) decreased edema from day 7. In rats with adjuvant-induced arthritis, only the ketoprofen patch significantly decreased edema after 2 weeks of application. In the skin permeation study, the ketoprofen preparations showed higher skin permeability compared with the other NSAID preparations. These results suggested that ketoprofen preparations had the most potent anti-inflammatory and analgesic activity related to good skin permeability. Efficacy of the ketoprofen patch was comparable to or better than that of ketoprofen gel at a lower dose and frequency of administration. Ketoprofen products, especially the patch preparation, could be useful for treating inflammatory pain in diseases like osteoarthritis and rheumatoid arthritis.
authors.affiliation: Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, Tamagawa-cho, Minami-ku, Fukuoka, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sakurada
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D002351:Carrageenan; D015232:Dinoprostone / Q000378:metabolism; D005060:Europe; D005260:Female; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D015003:Yeasts
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D015232:Dinoprostone