Protein Binding of Nonsteroidal Anti-inflammatory Agents. II. Effects of Various Drugs on Protein Binding of Salicylic Acid

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Abstract
The effect of 5 nonsteroidal anti-inflammatory agents and 7 sulfonamides on the binding of salicylic acid to bovine serum albumin (BSA, fraction V) was examined by the equilibrium dialysis method at pH 7.4 and 37.degree. C. Most of anti-inflammatory agents, which have a high affinity for BSA, strongly displaced salicylic acid. Sulfonamide derivatives reduced the binding of salicylic acid through their effect of displacement was less than that of anti-inflammatory agents. When the percentage of displacement for salicylic acid was plotted against log (.SIGMA.nk) which represents a binding ability of the displacing agent itself, a sigmoid curve was obtained. The amount of displacement apparently tends to correspond to the binding ability of the displacing agent and becomes progressively greater as log (.SIGMA.nk) becomes larger than that of salicylic acid. In the wide range of salicylic acid concentration (0.1-2.5 .times. 10-3 M) naproxen and flurbiprofen showed patterns of displacement for salicylic acid different from that of other displacing agents. They seemingly have binding mechanisms different from the others including salicylic acid.