title: Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model.
abstract: Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50  = 8.97 nM) and COX-2 (IC50  = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically.
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Toda
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Hori
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mitani
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ichihara
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Development Headquarters, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Endo
authors.affiliation: Product Management Division, Taisho Toyama Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Futaki
authors.affiliation: Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kaku
authors.affiliation: Development Headquarters, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Otsuka
authors.affiliation: Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000287:Administration, Topical; D000700:Analgesics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D005480:Flurbiprofen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: S(+)-flurbiprofen; analgesic; nonsteroidal anti-inflammatory drugs