Stereoselective disposition of fenoprofen in plasma and synovial fluid of patients with rheumathoid arthritis

Authors

  • Carolina De Miranda Silva,

    1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil
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  • Maria Paula Marques,

    1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil
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  • Giuliano Rodrigo Barissa,

    1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil
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  • Eduardo Antônio Donadi,

    1. Faculdade de Medicina de Ribeirão Preto-Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil
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  • Lucienir Maria Da Silva,

    1. Faculdade de Medicina de Ribeirão Preto-Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil
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  • Vera Lucia Lanchote

    Corresponding author
    1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil
    • Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Departamento de Análises Clínicas, Toxicológicas and Bromatológicas, Avenida do Café s.n. Campus da USP, 14040-903, Ribeirão Preto, SP, Brazil
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Abstract

The simultaneous disposition of fenoprofen enantiomers in synovial fluid and plasma was studied in 11 patients with arthritis and chronic knee effusions treated with a single oral dose of 600 mg rac-fenoprofen. A plasma sample and a synovial fluid sample were collected simultaneously from each patient up to 16 h after the administration of fenoprofen. A stereospecific assay for fenoprofen using LC–MS–MS was developed and applied successfully to the analysis of the enantiomers in plasma (LOQ = 10 ng of each enantiomer/ml) and synovial fluid (LOQ = 25 ng of each enantiomer/ml). The values of the area under the curve (AUC) for the S-(+)-fenoprofen eutomer were ∼2.5 times higher in plasma than in synovial fluid (256 vs 104 μg h/ml), while the values for the R-(−)-fenoprofen distomer were about four times higher in plasma than in synovial fluid (42.5 vs 10.5 μg h/ml). These data demonstrate accumulation of the S-(+)-fenoprofen eutomer in plasma and in synovial fluid, with concentrations versus time AUC (+)/(−) ratios of 6.0 in plasma and 9.9 in synovial fluid, suggesting a greater accumulation of the eutomer at the active site represented by synovial fluid than in plasma. This result demonstrates the importance of enantioselective methods and of analysis of synovial fluid rather than plasma in studies of the pharmacokinetics–pharmacodynamics of fenoprofen. Chirality, 2007. © 2007 Wiley-Liss, Inc.

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