A comparison of plasma and synovial fluid profiles of standard and controlled-release formulations of ketoprofen in patients with rheumatoid arthritis

Abstract

The plasma and synovial fluid profiles of standard and controlled-release formulations of ketoprofen were compared in 8 patients with rheumatoid arthritis. During chronic dosing with both forms of ketoprofen, peak drug concentrations were lower and occurred later in the synovial fluid than in the plasma. These findings were more pronounced in the case of the controlled-release formulation. The apparent elimination half-life of standard ketoprofen in synovial fluid was prolonged compared to its half-life in plasma, a finding which has not been previously documented. This may explain the clinical observation that, despite a very short plasma elimination half-life, standard ketoprofen exerts a satisfactory therapeutic effect when given twice daily. There was no accumulation of ketoprofen from either formulation in synovial fluid after steady state had been achieved. It is suggested that future pharmacological studies with anti-inflammatory agents should include both synovial fluid and plasma concentration data.