Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model

Masanori Sugimoto, Yoshihisa Toda, Miyuki Hori, Akiko Mitani, Takahiro Ichihara, Shingo Sekine, Takuya Hirose, Hiromi Endo, Nobuko Futaki, Shinsuke Kaku, Noboru Otsuka, Hideo Matsumoto

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

(Table Presented) 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.

Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalDrug Development Research
Volume77
Issue number1
DOIs
Publication statusPublished - 2016 Feb 1

Fingerprint

Flurbiprofen
Experimental Arthritis
Ketoprofen
Analgesics
Pain
Prostaglandin-Endoperoxide Synthases
Dinoprostone
Inhibitory Concentration 50
Skin Absorption
Cyclooxygenase 1
Pain Threshold
Cyclooxygenase Inhibitors
Hyperalgesia
Non-Steroidal Anti-Inflammatory Agents
Cyclooxygenase 2
Mycobacterium tuberculosis
Recombinant Proteins
Prostaglandins
Anti-Inflammatory Agents
loxoprofen

Keywords

  • analgesic
  • nonsteroidal anti-inflammatory drugs
  • S(+)-flurbiprofen

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model. / Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo.

In: Drug Development Research, Vol. 77, No. 1, 01.02.2016, p. 20-28.

Research output: Contribution to journalArticle

Sugimoto, M, Toda, Y, Hori, M, Mitani, A, Ichihara, T, Sekine, S, Hirose, T, Endo, H, Futaki, N, Kaku, S, Otsuka, N & Matsumoto, H 2016, 'Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model', Drug Development Research, vol. 77, no. 1, pp. 20-28. https://doi.org/10.1002/ddr.21288
Sugimoto, Masanori ; Toda, Yoshihisa ; Hori, Miyuki ; Mitani, Akiko ; Ichihara, Takahiro ; Sekine, Shingo ; Hirose, Takuya ; Endo, Hiromi ; Futaki, Nobuko ; Kaku, Shinsuke ; Otsuka, Noboru ; Matsumoto, Hideo. / Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model. In: Drug Development Research. 2016 ; Vol. 77, No. 1. pp. 20-28.
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