Plasma and synovial fluid kinetics of flurbiprofen in rheumatoid arthritis

Clinical assessment, plasma and synovial fluid kinetics were studied in 29 rheumatoid patients receiving 100 mg flurbiprofen twice daily. Clinical assessment and pharmacokinetic measurements varied widely within the group of patients. The average values for plasma clearance, volume of distribution and elimination halflife of flurbiprofen were 0.65 +/- 0.24 ml min-1 kg-1, 0.160 +/- 0.093 l kg-1 and 3.1 +/- 1.7 h, respectively. Synovial fluid drug concentrations peaked later and were lower than corresponding plasma concentrations: 5.2 h and 4.4 mg l-1 as against 1.49 h and 12.5 mg l-1, respectively. At 48 h after an oral dose of flurbiprofen, all the drug had been cleared from the synovial fluid. Synovial fluid drug concentrations were not related to synovial fluid albumin concentration or pH. There was a weak relationship between synovial fluid drug concentration and the thermographic measurements of disease activity. The fractions of flurbiprofen not bound to protein in synovial fluid and plasma were not significantly different. A simple model is proposed to account for the plasma and synovial fluid pharmacokinetics.