Kinetics of the Binding of Salicylazosulfapyridine to Human Serum Albumin

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Abstract
In order to elucidate the possibility of the dissociation rate of drugs from plasma proteins presenting a rate limiting step in the elimination of drugs by secretion (renal or biliary) and metabolism, the kineics of salicylazosulfapyridine (SASP) binding to human serum albumin (HSA) was investigated by stopped-flow photometry. Equilibrium dialysis showed that HSA has 3 classes of binding sites for SASP with 0.93, 2.3 and 8.4 sites, respectively, and association constants of 2.1 .cntdot. 106, 1.4 .cntdot. 105 and 3.0 .times. 103 M-1, respectively. The association rate constants for the 1st and 2nd classes are 4.4 .times. 106 and 1.5 .cntdot. 107 M-1 s-1, and the dissociation rate constants are 2.1 and 109 s-1. At SASP concentrations resulting from the usual therapeutic doses about 83% bind to the 1st class binding sites. The dissociation half time for this class being 0.34 s leads to the conclusion that dissociation rates of this order of magnitude are unlikely to reduce the rate of metabolism or biliary secretion, whereas it may reduce renal tubular secretion. Whether this is the case depends on the intrinsic rate constant of secretion.