Studies on protein binding of antibiotics. I. Effect of cefazolin on protein binding and pharmacokinetics of cefoperazone

The effect of cefazolin (CEZ) on the protein binding and the pharmacokinetics of cefoperazone (T-1551) was investigated. For the simultaneous determination of T-1551 and CEZ, high pressure liquid chromatography (HPLC) was used. The extent of protein binding, the number of binding sites and the association constant to human serum albumin were 90.4%, 0.87 and 2.16 X 10(4) in T-1551, and 89.2%, 0.78 and 2.46 X 10(4) in CEZ, respectively. T-1551 and CEZ appeared to bind to the same site on the protein, since each drug competitively inhibited the binding of the other to serum protein. The mode of the binding of T-1551 to serum protein was similar to that of CEZ. When T-1551 and CEZ were co-administered, the serum level of T-1551 was lower than that with the single administration, while, urinary excretion was higher. These results suggested that the concomitantly administered drugs influenced one another's binding to serum protein in vivo and subsequently an increase in the concentration of the unbound drug in the serum made the drug available for glomerular filtration. It seemed that the high protein binding of T-1551 to serum was an important factor affecting its pharmacokinetics.