The diffusion of nimesulide gel into synovial fluid: a comparison between administration routes

BACKGROUND: Nimesulide is available in gel formulation and applied mainly for topical pain management. However, its passage to the synovial fluid is not yet clear. The aim of this study was to evaluate if topical administered nimesulide passes into the synovial fluid and to compare its concentration with the oral nimesulide administration regimen. METHODS: Synovia and plasma nimesulide concentrations were investigated in patients after topical (Sulidin gel 1%) and oral (Mesulid tablet) drug administration. 34 adult outpatients who were scheduled to have an arthroscopic knee examination for mainly meniscal tears repair and who had knee pain during this period were enrolled in the first part of the study. One group received topical nimesulide gel to the skin of the knee whereas the second group received oral 2 x 100 mg nimesulide tablets, 4-7 days before the planned arthroscopy. Synovial fluid and plasma samples were taken simultaneously during the arthroscopy and analyzed using HPLC. In addition, an open-label pilot study was performed to investigate the efficacy and safety of 1-week administration of nimesulide gel. 63 knee osteoarthritis patients were asked to complete the WOMAC Osteoarthritis Index questionnaire before and 1 week after use of Sulidin gel applied 3 times daily. RESULTS: Synovia and plasma nimesulide concentrations were 19.7 +/- 8.6, 11.8 +/- 3.0 and 1958.8 +/- 397.5, 3631.9 +/- 799.3 ng/ ml for topical and oral administration groups, respectively. There was a significant (paired Student's t-test) improvement after 1 week nimesulide treatment in all WOMAC Osteoarthritis Index parameters measured. CONCLUSION: Nimesulide passes into the synovial fluid after topical administration and may have potential benefits in knee osteoarthritis treatment. The actual efficacy and safety of topical nimesulide gel administration should be investigated in a long-term, randomized, placebo-controlled clinical trial.