The effects of pH, calcium and chloride ions on the binding of tolmetin to human serum albumin: circular dichroic, dialysis and fluorometric measurements.

The binding of the non-steroidal anti-inflammatory drug, tolmetin (1-methyl-5-p-toluoylpyrrole-2-acetic acid) to human serum albumin (HSA) has been shown by circular dichroism, fluorescence and equilibrium dialysis to be dependent on the N-B conformational change of the albumin. The influence of calcium and chloride ions on the interaction was also investigated using the same techniques. Experiments suggested that calcium ions increased the binding constant of tolmetin to HSA whereas chloride ions decreased it. The displacement study showed that tolmetin caused a significant increase in the affinity of diazepam to HSA whereas it decreased the binding of warfarin to HSA. Tolmetin seems to cause an allosteric change in the diazepam binding site in spite of it sharing a primary site with warfarin.