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: Masanori Sugimoto, Yoshihisa Toda, Miyuki Hori, Akiko Mitani, Takahiro Ichihara, Shingo Sekine, Takuya Hirose, Hiromi Endo, Nobuko Futaki, Shinsuke Kaku, Noboru Otsuka, Hideo Matsumoto
• Journal: Drug development research (Drug Dev Res) Vol. 77 Issue 1 Pg. 20-8 (Feb 2016) ISSN: 1098-2299 [Electronic] United States
• PMID: 26763139 (Publication Type: Journal Article)
• Copyright: © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

Chemical References

• Analgesics
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase Inhibitors
• Flurbiprofen
• Cyclooxygenase 1
• Cyclooxygenase 2
• PTGS1 protein, human
• PTGS2 protein, human
• Dinoprostone

Topics

• Administration, Topical
• Analgesics (administration & dosage, pharmacokinetics, pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacokinetics, pharmacology)
• Arthritis, Experimental (drug therapy, immunology)
• Cyclooxygenase 1 (metabolism)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase Inhibitors (administration & dosage, pharmacokinetics, pharmacology)
• Dinoprostone (metabolism)
• Disease Models, Animal
• Flurbiprofen (administration & dosage, pharmacokinetics, pharmacology)
• Humans
• Male
• Pain Threshold (drug effects)
• Rats
• Rats, Sprague-Dawley