SODIUM NAPROXEN - CONCENTRATION AND EFFECT ON INFLAMMATORY RESPONSE MEDIATORS IN HUMAN RHEUMATOID SYNOVIAL-FLUID

Twelve patients suffering from rheumatoid arthritis and having swollen knees were treated with 1.1 g/day of sodium naproxen administered in one dose, daily for 5 days. The 72-h wash-out period was verified by t he absence of any nonsteroidal anti-inflammatory drug using a HPLC scr eening. Flood and synovial fluid samples were drawn just before treatm ent and 24 h after the last dose. Eicosanoids (PGE(2), 6-keto-PGF(1) a lpha, TXB(2), LTB(4), LTC(4)) in synovial fluid were determined by imm unoenzymatic assays. In plasma and synovial fluid, hyaluronic acid was assayed by radiometric assay and sodium naproxen by HPLC. Free drug w as determined by equilibrium dialysis. Statistical analysis used nonpa rametric tests. Pain relief (evaluated on a visual scale), morning sti ffness, and scores on the Lee and Ritchie indices all decreased signif icantly, as did PGE(2) and LTB(4) concentrations. The decrease in 6-ke to-PGF(1) alpha and TXB(2) was not significant. No significant change was found for LTC(4) and hyaluronic acid. Total concentrations of sodi um naproxen were equivalent in plasma (16.1 mu g.ml(-1)) and synovial fluid (18.9 mu g.ml(-1)). Free fractions were significantly higher in synovial fluid (0.14%) than in plasma (0.11%), as shown by binding of the drug to human serum albumin, at various protein concentrations. In terestingly, the clinical efficacy, as shown by decreases in morning s tiffness and in the Lee index score, correlated with the free concentr ation of naproxen in synovial fluid.