Zomepirac--aspirin interactions in man.

The pharmacokinetic interaction between zomepirac and aspirin was studied in 12 healthy males who received a single dose of 100 mg zomepirac sodium on days 1 and 5 and 975 mg aspirin every 6 hours on days 2 to 5. The results indicated that in the presence of salicylate, the peak concentration of zomepirac was depressed; peak time, AUC(0-24 hr), and clearance of total drug remained unchanged. Percentage unbound zomepirac was increased twofold. In the presence of zomepirac, the peak concentration and AUC of salicylate were increased and clearance decreased. The data suggest that zomepirac and salicylate compete with each other for the enzymes and/or cofactors involved in glucuronidation. This competition for metabolic clearance offsets the consequences of the zomepirac-salicylate interactions at the plasma protein binding sites. However, in light of increased unbound zomepirac as well as decreased clearance of unbound drug, concomitant therapy of zomepirac and aspirin is not advised.