Interaction studies in the rat and healthy human volunteers have shown that protein binding of diclofenac is reduced by the addition of salicylic acid causing an increased free drug level of diclofenac. The diclofenac area under curve (AUC) is also reduced by approximately one-third in the presence of salicylate.
We have performed a crossover comparison of soluble aspirin, diclofenac and the two drugs in combination in patients with rheumatoid arthritis to determine whether this had clinical relevance.
36 patients entered the study. There was a high dropout rate on aspirin alone but analysis of completors (22 patients) showed diclofenac either alone or in combination to be superior to aspirin alone on two of the five clinical parameters measured.
There was no significant difference between disclofenac and aspirin+diclofenac. We thus found no clinical manifestations of the pharmacokinetic interaction.