Penetration of topical diclofenac sodium 4 % spray gel into the synovial tissue and synovial fluid of the knee: a randomised clinical trial

Knee Surg Sports Traumatol Arthrosc. 2014 Feb;22(2):345-50. doi: 10.1007/s00167-013-2408-0. Epub 2013 Jan 22.


Purpose: 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / blood
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Chromatography, Liquid
  • Diclofenac / blood
  • Diclofenac / pharmacokinetics*
  • Diclofenac / therapeutic use
  • Female
  • Gels
  • Humans
  • Knee Joint / metabolism*
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / metabolism
  • Synovial Fluid / metabolism
  • Synovial Membrane / metabolism*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Gels
  • Diclofenac