Binding of sulfinpyrazone and its metabolites in human serum and in solutions of human serum albumin.

Abstract

The binding of sulfinpyrazone its sulfone metabolite and its sulfide metabolite to serum protein was studied by equilibrium dialysis. At 20 micrograms/ml 99.1% of the parent compound was bound in serum, whereas 99.8% of the sulfide and 98.3% of the sulfone were bound at this concentration. The binding of the three compounds were studied in diluted serum and in solutions of human serum albumin (HSA). There was no evidence of binding to proteins other than albumin. The association constants to primary and secondary binding sites and the number of binding sites were calculated. For the sulfide a lower K1-value in serum (0.76 . 10(6)M-1) than in the HSA solution (1.8 . 10(6)M-1) indicated the possible presence of a competitively bound substance in serum. In undiluted serum no displacing effect of the sulfide on sulfinpyrazone binding was found when both compounds were present in a concentration of 20 micrograms/ml, but in a HSA solution a pronounced sulfide induced displacement of the sulfinpyrazone from its primary binding site was shown. Acetylation of HSA depressed the binding of sulfinpyrazone but in undiluted serum there was no other effect on sulfinpyrazone binding by the addition of acetylsalicylic acid than could be explained by the displacing effect of salicylic acid. At concentrations of 20 micrograms/ml of sulfinpyrazone and above 50 micrograms/ml of the displacing agent significant displacement was demonstrated with phenylbutazone, tolbutamide and salicylic acid.