title: Penetration of topical diclofenac sodium 4 % spray gel into the synovial tissue and synovial fluid of the knee: a randomised clinical trial.
abstract: OBJECTIVE
  The present study was designed to evaluate the penetration of diclofenac sodium 4 % spray gel in synovial tissue, synovial fluid and blood plasma after topical application in subjects with joint effusions and planned total knee arthroplasty (TKA) due to osteoarthritis.
  
  
  METHODS
  A total of 39 patients were randomised to two- or three-times daily application of diclofenac sodium 4 % spray gel to knees requiring surgery over a treatment period of 3 days. Within 8 h after the last application, TKA was conducted, and the diclofenac concentrations in synovial tissue, synovial fluid and blood plasma were measured by liquid chromatography.
  
  
  RESULTS
  The median diclofenac concentration was approximately 10-20-fold higher in synovial tissue (36.2 and 42.8 ng/g) than in synovial fluid (2.6 and 2.8 ng/mL) or plasma (3.9 and 4.1 ng/mL) in both treatment groups. Dose proportionality for any compartment or treatment groups could not be detected. Treatment-related adverse events were noted in two cases and limited to skin reactions.
  
  
  CONCLUSIONS
  Diclofenac sodium 4 % spray gel was found to penetrate the skin locally in substantial amounts and thus reach the desired target tissue. Concentrations were not dose-dependent, and application was well tolerated by 97.4 % of patients. Topical application of diclofenac should be considered a valuable alternative to systemic NSAID therapy in the initial treatment of osteoarthritis.
authors: Department of Orthopaedics and Rheumatology, University Hospital Marburg, Baldingerstrasse, 35043, Marburg, Germany, efet@med.uni-marburg.de.
authors: Turgay
authors: T
authors: Efe
authors: Ercan
authors: E
authors: Sagnak
authors: Philip P
authors: PP
authors: Roessler
authors: Alan
authors: A
authors: Getgood
authors: Thilo
authors: T
authors: Patzer
authors: Susanne
authors: S
authors: Fuchs-Winkelmann
authors: Christian D
authors: CD
authors: Peterlein
authors: Markus D
authors: MD
authors: Schofer
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D004008:Diclofenac / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005782:Gels; D006801:Humans; D007719:Knee Joint / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D004008:Diclofenac