A thermodynamic approach to the binding mechanisms of cefotaxime to serum albumins.
The interaction between cefotaxime and the serum albumin of several mammalian species (swine, rabbits, and sheep) at the albumin concentration of 5 x 10(-5) M was studied. Ultrafiltration and spectrophotometric determination of the free antibiotic in the filtrate were used. Binding percentages were determined, and the binding constants and number of sites at various temperatures were calculated. An increase in binding constants, especially in sheep albumin, and an increase in the number of sites from two to three were observed when compared to the results obtained at the physiological albumin concentration. The thermodynamic parameters of interaction varied between the following values: change in Gibbs energy, between -5.7 and -6.4 kcal.mol-1; change in enthalpy, between -6.7 and -9.6 kcal.mol-1; and change in entropy, between -3.1 and -11.2 entropy units. The binding constants increased considerably as the ionic strength of the solution decreased although the number of binding sites remained unchanged. These results indicate the existence of ionic and hydrogen bonds. The possibility of a small contribution from hydrophobic bonds cannot be ruled out.
Fernandez
G M
GM
Departamento de Físiça y Química, Facultad de Biología, Universidad de León, Spain.
Lumbreras
J M
JM
Ordonez
D
D
D000818:Animals; D002439:Cefotaxime / Q000097:blood* / Q000493:pharmacokinetics; D011485:Protein Binding; D011817:Rabbits; D017457:Receptors, Albumin / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D012756:Sheep; D013045:Species Specificity; D013053:Spectrophotometry; D013552:Swine; D013696:Temperature; D013816:Thermodynamics; D014462:Ultrafiltration
D017457:Receptors, Albumin; D012709:Serum Albumin; D002439:Cefotaxime