| Abstract: | The binding of salicylates by human serum albumin was analyzed by use of a computer program using previously published association constants and binding capacities for the two sets of binding sites on the protein. The analysis consisted of computing free and bound salicylates for a range of therapeutic and toxic concentration from 181 to 7246 mumole/L (25 to 1000 mg/L). At low and therapeutic levels the total amount of bound drug would exceed the amount of free drug. At higher levels, which included therapeutic and toxic ranges, the amount of free drug plasma, up to 2000 mumole/L the high affinity sites (Site 1), would bind most of the drug, but as the concentration of drug increased this site would approach saturation and the low affinity Site 2 would bind increasing amounts of salicylate. At high salicylate levels the amount of drug bound by the low affinity sites. Computation also showed that when the total amount of protein in the analysis was reduced, from 5, 4, 3, to 2 gm%, as in hypoalbuminemia, the total amount of drug bound by the protein would decrease and the quantity of free drug would increase. The amount of drug bound by each of the two sets of sites also fell as the concentration of protein decreased. Some of the possible clinical implications of these findings are discussed. |
