Osmosin: its effect on plasma and synovial fluid kinetics of indomethacin

Summary

‘Osmosin’ (sodium indomethacin trihydrate, now withdrawn) produced a constant rate of release of indomethacin into the gut. Paired plasma and synovial fluid samples were obtained at regular intervals following a single dose of ‘Osmosin’ (19 patients) and after continuous daily dosing (15 patients). Indomethacin is rapidly absorbed and plasma concentrations maintained in the range 0.3 to 0.6 µg/ml after the first 4 h. Equilibrium between plasma and synovial fluid occurs, with SF/plasma ratios 0.74 to 0.82 12–24 h after a single dose and up to 0.96 thereafter. The indomethacin synovial fluid/plasma profile is changed by Osmosin from the pattern of a short half-life drug to the pattern typical of a long half-life drug. Results from serial samples obtained by use of indwelling cannulae (in vein and knee joint) show close agreement with our single paired sampling technique. Our method may have theoretical disadvantages but it has many practical advantages.