Abstract
Binding of six nonsteroidal anti-inflammatory agents, flutenamic acid, flurbiprofen, indomethacin, phenylbutazone, naproxen, and salicylic acid, to bovine serum albumin was examined using the equilibrium dialysis method at pH 7.4 and 37°. The nonlinear Scatch ard plots were obtained from the binding data except for indomethacin. On the assumption that there are two classes of binding sites on the protein molecule, the binding parameters, n1, n2, k1, and k2, were estimated. The partition coefficient, Kp, of these agents to several organic solvents was measured but there was no correlation between Kp and binding parameters. The theoretical percentage of drug free against total concentration in serum was calculated from the binding parameters assuming the concentration of human serum albumin as 4.11 g/dl. It was found that flufenamic acid and indomethacin strongly bind to the protein and the free fraction of these drugs exist within 1% over the therapeutic range. Phenylbutazone and naproxen also bind to the protein strongly, but the saturable nature of the binding sites with increasing drug concentration was observed.
