INVITRO PROTEIN-BINDING OF CEFONICID AND CEFUROXIME IN ADULT AND NEONATAL SERA

The levels of in vitro protein binding of cefonicid and cefuroxime in human adult and neonatal sera were compared. Binding parameters for ea ch drug were determined within the concentration range of 25 to 3,000 mug/ml. Cefonicid exhibited concentration-dependent protein binding in both types of sera, with more extensive binding in adult serum at all concentrations. Two classes of binding sites were found: a high-affin ity, saturable site and a low-affinity, nonspecific site. Cefuroxime a lso showed two-class, concentration-dependent protein binding in adult serum, but binding in neonatal serum was to a single class and was in dependent of drug concentration. Parameters for class 1 binding sites for cefonicid indicated one binding site per albumin molecule in both adult and neonatal sera, with association constants of 7.0 x 10(4) and 1.3 x 10(4) M-1, respectively. These parameters were also derived for cefuroxime in adult serum and were 0.15 and 7.1 x 10(4) M-1, respecti vely. In neonatal serum, the combined value (number of binding sites p er molecule x equilibrium association constant) was similar to combine d values calculated for class 2 binding sites for cefuroxime in adult serum and for cefonicid in neonatal serum (287 versus 195 and 261 M-1, respectively). Cephalosporins have been shown to compete with bilirub in for albumin binding sites. Lower levels of protein binding of cefur oxime in the therapeutic range may mean a lower potential for drug dis placement of bilirubin in neonates, on the basis of these results. It may be prudent to select less highly protein-bound agents when treatin g neonatal infections.