title: Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans.
abstract: OBJECTIVE
  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.
authors.affiliation: Development Headquarters, Taisho Pharmaceutical Co. Ltd, 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yataba
authors.affiliation: Development Headquarters, Taisho Pharmaceutical Co. Ltd, 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan. n-otsuka@so.taisho.co.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Otsuka
authors.affiliation: Development Headquarters, Taisho Pharmaceutical Co. Ltd, 3-24-1 Takada, Toshima-ku, Tokyo, 170-8633, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsushita
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kamezawa
authors.affiliation: Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan.
authors.forename: Ichimaro
authors.initials: I
authors.lastname: Yamada
authors.affiliation: Sapporo Tsukisamu Chuo Orthopedics, Sapporo, Japan.
authors.forename: Sigeru
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Faculty of Health Science, Teikyo Heisei University, Ichihara, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Uebaba
authors.affiliation: Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Orthopedics Surgery, School of Medicine, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hoshino
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000378:metabolism*; D016037:Single-Blind Method; D013583:Synovial Membrane / Q000378:metabolism*; D057968:Transdermal Patch; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005480:Flurbiprofen
keywords: Pharmacokinetics; S-flurbiprofen; Synovial tissue; Tissue concentration; Topical NSAIDs