Tissue Absorption and Distribution of Ketoprofen after Patch Application in Subjects Undergoing Knee Arthroscopy or Endoscopic Carpal Ligament Release

The diffusion into the target tissues of ketoprofen (CAS 22071-15-4), a widely used nonsteroidal anti-inflammatory drug, from a new topical patch has been studied after repeated patch application in comparison with its plasma level. Ten patients (5 women and 5 men) with a mean age of 45.0 ± 12.3 years (mean ± SD), scheduled for arthroscopic meniscectomy (5 subjects) or endoscopic carpal tunnel decompression (5 subjects), were asked to apply one patch with 100 mg ketoprofen on the affected body site once a day during the 6 days before the scheduled surgery. The last patch was kept for 6 h, and removed just a few minutes before surgery, when venous blood was drawn. Biopsies of the synovial tissue of the medial compartment and of the anterior fat pad (Hoffa’s tissue) or of the ulnar bursa were taken during knee arthroscopy or endoscopic carpal tunnel release, respectively. An average plasma value of 52.8 ± 30.1 (SD) ng/ml of ketoprofen was obtained in the 10 patients. The tissue concentrations of ketoprofen in the 5 subjects undergoing knee arthroscopy were 27.9 ± 26.1 ng/g (range 7.2-67.1 ng/g) in the anterior fat pad and 239.0 ± 163.0 ng/g (range 20.0-430.5 ng/ g) in the synovial tissue. Drug concentrations up to 1000 times higher were found in the tendon sheath tissue of the ulnar bursa of the five patients undergoing endoscopic carpal tunnel release: average values of 20 107 ± 7359 ng/g (range 13 004-32 578 ng/g) were obtained in this tissue. Data observed in this trial are consistent with those previously published by other authors, and demonstrate that ketoprofen applied on the skin is able to enter the subcutaneous and intra-artic-ular tissues, reaching concentrations markedly higher than in plasma, and is further able to produce the desired pharmacological activity in situ, whereas plasma concentrations are too low to produce any systemic activity or side effect.