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  • 1
    ISSN: 1432-1041
    Keywords: Naproxen ; Synovial fluid ; Rheumatoid arthritis ; NSAIDs ; eicosanoid ; concentration/effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract 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 the absence of any nonsteroidal anti-inflammatory drug using a HPLC screening. Blood and synovial fluid samples were drawn just before treatment and 24 h after the last dose. Eicosanoids (PGE2, 6-keto-PGF1α, TXB2, LTB4, LTC4) in synovial fluid were determined by immunoenzy-matic assays. In plasma and synovial fluid, hyaluronic acid was assayed by radiometric assay and sodium naproxen by HPLC. Free drug was determined by equilibrium dialysis. Statistical analysis used nonparametric tests. Pain relief (evaluated on a visual scale), morning stiffness, and scores on the Lee and Ritchie indices all decreased significantly, as did PGE2 and LTB4 concentrations. The decrease in 6-keto-PGF1α and TXB2 was not significant. No significant change was found for LTC4 and hyaluronic acid. Total concentrations of sodium naproxen were equivalent in plasma (16.1 μg·ml−1) and synovial fluid (18.9 μg·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. Interestingly, the clinical efficacy, as shown by decreases in morning stiffness and in the Lee index score, correlated with the free concentration of naproxen in synovial fluid.
    Type of Medium: Electronic Resource
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