Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication.

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

De Miranda Silva C, Marques MP, Barissa GR, Donadi EA, Da Silva LM, Lanchote VL

Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil.

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 approximately 2.5 times higher in plasma than in synovial fluid (256 vs 104 microg 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 microg 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.

Published 2 April 2007 in Chirality, 19(4): 255-63.
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