Interaction of some isoxazolyl penicillins with human serum albumin

Abstract

The nature and magnitude of the interaction of penicillins with serum albumin has important pharmacokinetic and pharmacodynamic implications. Mechanism of interaction of three isoxazolyl penicillins, cloxacillin sodium, dicloxacillin sodium and flucloxacillin sodium with Human Serum Albumin (HSA) has been studied using fluorescence spectroscopic technique. Quenching of tryptophan fluorescence of HSA under different conditions and fluorescent probe displacement studies were carried out. The stoichiometry of the interaction was found to be 1:1 in each case. The association constants were of the order of 104 in the case of all the drug samples. The order of association constants was dicloxacillin sodium > flucloxacillin sodium>cloxacillin sodium. The nature of drug-protein interaction could be predicted from the thermodynamic parameters for the binding. The binding was predominantly through hydrophobic interactions in the case of cloxacillin. In the case of dicloxacillin and flucloxacillin, hydrogen bonding as well as hydrophobic interactions contributed to the interaction. Binding studies carried out in the presence of hydrophobic probe, ANS showed that the drugs and ANS do not share common site on the albumin molecule. Displacement of DSS from its binding site on albumin showed that site II is involved in binding. Stern-Volmer analysis of fluorescence data revealed that the tryptophan residues of serum albumin are not fully accessible to drugs, drug binding site is in close proximity to the tryptophan residues and predominantly static quenching mechanism is operative. © 2006 Asian Network for Scientific Information.