Drug-Biomacromolecule Interaction VIII

The effects of ionic strength and pH on the binding of cefazolin to bovine serum albumin (BSA) were studied by UV difference spectrophotometry. As ionic strength at constant pH and temperature increases, the apparent bining constant decreased but the number of binding sites remained almost constant at 2. The constancy of the number of binding sites with increasing the ionic strength suggests that purely electrostatic forces between BSA and drug do not have great importance in the drug binding, even though there is a decrease in the apparent binding constant. Thus, the effect of ionic strength on the interaction between drug and BSA may be explained by the changes in ionic atmosphere of the aggregated BSA molecules and competitive inhibition by phosphate ions. In addition, the higher apparent binding constant at high ionic strength is explained by conformational changes of BSA from its aggregate forms into subunits. The pH effects on the afinity of interactions indicated that the binding affinity of cefazoline is higher in the neutral region than in the alkaline region. An d at high pH value, the number of binding sites decreased from 2 to 1 because of the conformational change of BSA in the alkaline region.