Interaction of isoxicam with acetylsalicylic acid

Ten healthy male volunteers were given 200 mg p.o. of isoxicam after an overnight fast and the plasma concentrations over time followed for 96 h by h.p.l.c. Five days later enteric coated acetylsalicylic acid (ASA) 650 mg four times daily was started and continued for 10 days producing steady state trough plasma salicylate of 83 mg/l (range 21-133). A second 200 mg isoxicam dose was given 5 days after starting ASA and the plasma concentration time-curve again followed. After ASA, there was no change in lag time (0.54 vs 0.51 h), time to peak concentration (10 vs 10 h), or disappearance t1/2 (28.7 vs 31.0 h) however the peak isoxicam concentration and AUC were reduced 18 and 22% respectively (P less than 0.01). Plasma protein binding of isoxicam studied by equilibrium dialysis was 96 +/- 1% in the absence and 86 +/- 5% in the presence of ASA. The reduction in binding was unrelated to plasma SA concentrations achieved or observed reductions in AUC for plasma isoxicam. ASA decreased plasma isoxicam binding, peak plasma isoxicam concentrations and AUC without altering the apparent disappearance half-life of total plasma isoxicam after a single oral dose.