Interaction of cephalosporins with human and canine serum proteins.

The kinetic interaction of cephalothin and cefamandole with human serum protein and of cephalothin with canine serum protein was studied with use of a rate-of-dialysis method. Binding of antibiotic to serum proteins was complete in less than 1 min and was immediately reversible. Human serum bound 76.9% of cephalothin and 73.7% of cefamandole at 10 microgram/ml, and canine serum bound 41.3% of cephalothin at 10 microgram/ml when this technique was used. Quantitative binding determined by ultracentrifugation was 78.5% for cephalothin and 80.1% for cefamandole in human serum and 45.6% for cephalothin and 32.5% for cefazolin in canine serum. There was no delayed binding of these antibiotics to either human or canine serum. In addition, a large number of antibiotic-binding sites appeared to be present on both human and canine serum protein when the antibiotic concentration was increased to 10(5) microgram/ml.