[Trans-synovial kinetics of tiaprofenic acid]

The transsynovial distribution and tissue accumulation of tiaprofenic acid (Surgam)--a nonsteroidal anti-inflammatory agent--was studied in 55 patients scheduled for knee joint surgery. The patients suffering from rheumatoid arthritis (53), ankylosing spondylitis (1) or a chronicly irritated knee joint (1), received 300 mg of tiaprofenic acid b.i.d. starting 4 days prior to surgery. Samples of plasma, synovial fluid, fat, muscle, bone and synovial tissue were obtained simultaneously at defined times following the last dose. The samples were analyzed for tiaprofenic acid employing HPLC. Peak plasma concentrations of 28.6 micrograms/ml were achieved after 1 h, whereas synovial levels rose up to 2.8 micrograms/ml after 8 h. The time course of the concentration ratios indicates equilibration of both compartments 6 h following the last dose. Elimination occurs with half-lives of 1.9 h from plasma and 3.1 h from synovial fluid. During this period, synovial levels persist in a range sufficient for in vitro cyclooxygenase inhibition. In contrast, tiaprofenic acid does not exert marked tissue affinity, probably due to its hydrophilic properties.