Kinetics of the binding of salicylazosulfapyridine to human serum albumin

Acta Pharmacol Toxicol (Copenh). 1977 Nov;41(5):401-16. doi: 10.1111/j.1600-0773.1977.tb02151.x.

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 kinetics of salicylazosulfapyridine (SASP) binding to human serum albumin (HSA) has been investigated by stopped-flow photometry. Equilibrium dialysis showed that HSA has three classes of binding sites for SASP with 0.93, 2.3 and 8.4 sites, respectively, and association constants of 2.1.10(6), 1.4.10(5) and 3.0.10(3) M-1, respectively. The association rate constants for the first and second classes are 4.4.10(6) and 1.5.10(7) M-1 sec.-1, and the dissociation rate constants are 2.1 and 109 sec.-1. At SASP concentrations resulting from the usual therapeutic doses about 83% will bind to the first class binding sites. The dissociation "half time" for this class being 0.34 sec., 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.

MeSH terms

  • Half-Life
  • Humans
  • Models, Biological
  • Photometry
  • Protein Binding
  • Renal Dialysis
  • Serum Albumin / metabolism*
  • Spectrophotometry
  • Sulfasalazine / analysis
  • Sulfasalazine / blood*
  • Time Factors

Substances

  • Serum Albumin
  • Sulfasalazine