A THERMODYNAMIC APPROACH TO THE BINDING MECHANISMS OF CEFOTAXIME TO SERUM ALBUMINS

The interaction between cefotaxime and the serum albumin of several ma mmalian species (swine, rabbits, and sheep) at the albumin concentrati on of 5 x 10(-5) M was studied. Ultrafiltration and spectrophotometric determination of the free antibiotic in the filtrate were used. Bindi ng percentages were determined, and the binding constants and number o f sites at various temperatures were calculated. An increase in bindin g constants, especially in sheep albumin, and an increase in the numbe r of sites from two to three were observed when compared to the result s obtained at the physiological albumin concentration. The thermodynam ic parameters of interaction varied between the following values: chan ge in Gibbs energy, between -5.7 and -6.4 kcal . mol-1; change in enth alpy, between -6.7 and -9.6 kcal . mol-1; and change in entropy, betwe en -3.1 and -11.2 entropy units. The binding constants increased consi derably as the ionic strength of the solution decreased although the n umber of binding sites remained unchanged. These results indicate the existence of ionic and hydrogen bonds. The possibility of a small cont ribution from hydrophobic bonds cannot be ruled out.