Plasma protein binding and interaction studies with piroxicam.

The binding of non-steroidal antirheumatic drug piroxicam to human serum albumin, human plasma and serum has been studied by equilibrium dialysis at 22 degrees C, pH 7.4. The binding data were analyzed according to Scatchard model. The values of binding parameters obtained for human serum albumin are quite similar to those obtained for human plasma and serum (N1 = 0.3, K1 = 3.0 x 10(5) l/mol; N2 = 7, K2 = 3.5 x 10(3) l/mol). We suggest that piroxicam interacts with the albumin fraction in human plasma proteins. The displacement of piroxicam (in the therapeutical concentration of 4.5 x 10(5) mol/l) from the binding to human serum albumin and human plasma has been studied. The concentration of albumin and albumin fraction in plasma was 2.9 x 10(-4) mol/l. The displacement substances were drugs--diazepam, warfarin and salicylic acid, and endogenous substances-bilirubin and palmitic acid. Only in the presence of salicylic acid in high clinical concentration (14.5 x 10(-4) mol/l) and palmitic acid in the molar ratio to albumin 5:1, free piroxicam substantially increased, which may be of clinical significance. Other studied substances displaced piroxicam only in high concentrations exceeding the therapeutical and physiological range. The evidence was found for the similarity of piroxicam and warfarin high-affinity binding site.