Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans

Ikuko Yataba, Noboru Otsuka, Isao Matsushita, Miho Kamezawa, Ichimaro Yamada, Sigeru Sasaki, Kazuo Uebaba, Hideo Matsumoto, Yuichi Hoshino

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18 Citations (Scopus)

Abstract

Purpose: The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. Methods: Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. Results: Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-∞ were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p <0.001) higher, respectively, than those achieved by the FP patch. Conclusions: Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalEuropean Journal of Clinical Pharmacology
Volume72
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

Keywords

  • Pharmacokinetics
  • S-flurbiprofen
  • Synovial tissue
  • Tissue concentration
  • Topical NSAIDs

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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    Yataba, I., Otsuka, N., Matsushita, I., Kamezawa, M., Yamada, I., Sasaki, S., Uebaba, K., Matsumoto, H., & Hoshino, Y. (2016). Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans. European Journal of Clinical Pharmacology, 72(1), 53-59. https://doi.org/10.1007/s00228-015-1960-6