In vitro 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 each drug were determined within the concentration range of 25 to 3,000 micrograms/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-affinity, saturable site and a low-affinity, nonspecific site. Cefuroxime also showed two-class, concentration-dependent protein binding in adult serum, but binding in neonatal serum was to a single class and was independent 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, respectively. In neonatal serum, the combined value (number of binding sites per molecule x equilibrium association constant) was similar to combined 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 bilirubin for albumin binding sites. Lower levels of protein binding of cefuroxime in the therapeutic range may mean a lower potential for drug displacement of bilirubin in neonates, on the basis of these results. It may be prudent to select less highly protein-bound agents when treating neonatal infections.
Benson
J M
JM
College of Pharmacy, University of Georgia, Augusta.
Boudinot
F D
FD
Pennell
A T
AT
Cunningham
F E
FE
DiPiro
J T
JT
D000328:Adult; D000375:Aging / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism; D015790:Cefonicid / Q000097:blood*; D002444:Cefuroxime / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D011485:Protein Binding
D001798:Blood Proteins; D015790:Cefonicid; D002444:Cefuroxime