Diflunisal pharmacodynamics in experimental arthritis in rats

The analgesic response-serum concentration relationship (pharmacodynamics) of a representative nonsteroidal antiinflammatory drug, diflunisal, was examined after an acute dose in adjuvant arthritic and control rats. The analgesic response was 2-fold higher in the arthritic animals compared to controls. In parallel with this, there was a 2-fold increase in the serum free concentrations of diflunisal in the arthritic rats. Thus, the increase in diflunisal analgesic response in arthritis may be attributed to pharmacokinetic perturbations, resulting from alterations in serum protein binding and not to changes in drug pharmacodynamics. Endogenous binding inhibitors in adjuvant arthritis may contribute to the observed decreased in diflunisal protein binding.