title: A minimal impact of long-term S-flurbiprofen plaster application on kidney function in osteoarthritis patients.
abstract: BACKGROUND
  The number of kidney injury due to nonsteroidal anti-inflammatory drugs (NSAIDs) is the largest among drug-induced kidney diseases. Newly developed NSAID plaster containing S-flurbiprofen (SFP) shows innovative percutaneous absorption. However, systemic exposure to SFP following the repeated application of 80 mg/day was estimated as comparable to that of oral 120 mg/day flurbiprofen and prolonged use of topical NSAIDs is common in clinical practice. Thus, we report the safety focusing on the kidney function after long-term application of SFP plaster (SFPP).
  
  
  METHODS
  A total of 201 osteoarthritis patients (mean age; 66.3, 151 females, mean estimated glomerular filtration rate; 74.6 mL/min/1.73 mm2) were applied 40 or 80 mg SFPP for 52 weeks, and kidney function was examined by blood urea nitrogen (BUN), serum creatinine (SCr), eGFR, and urinalysis.
  
  
  RESULTS
  161 (80.1%) patients completed 52-week application. In both groups of 40 and 80 mg, small but statistically significant increases were observed in BUN (mean 1.91 and 1.89 mg/dL, p < 0.05) and SCr (mean 0.019 and 0.022 mg/dL, p < 0.05). Although abnormal changes in laboratory test for renal function were observed in seven patients, all the changes were small and subclinical. Acute kidney injury was observed in two patients. Meanwhile, the investigators denied the relevance of SFPP according to the clinical course.
  
  
  CONCLUSIONS
  Toward the end of 52-week application, a statistically significant increase in SCr was observed in both 40 and 80 mg, but increment was small and subclinical. Attention should be paid to kidney function when applying SFPP to patients with multiple risk factors.
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.identifier: http://orcid.org/0000-0002-9834-8384
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: 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.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsushita
authors.affiliation: Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Orthopedics Surgery, School of Medicine, Jichi Medical University, 3111-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Terada
mesh_terms: D000279:Administration, Cutaneous; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000139:chemically induced*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005480:Flurbiprofen
keywords: Acute kidney injury; Drug-induced kidney disease; Kidney function; Long-term safety; Nonsteroidal anti-inflammatory drugs; S-flurbiprofen