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The drug-protein interactions between cefoperazone (CPZ) and novobiocin (NB), and between cefazolin (CEZ) and NB were investigated. Though there was a remarkable reduction of CPZ or CEZ binding to rabbit serum and human serum albumin with increases in drug concentrations above 3.0x10-4M (CPZ: 200 microgram/ml, CEZ: 140 microgram/ml), NB binding was not affected. In addition, when CPZ or CEZ was added to the NB solution, NB binding was not altered and remained above 90%. Therefore, it was evident that NB had a high capacity for binding to protein, compared with CPZ or CEZ. From the competitive study, the main binding site of NB to protein appeared to differ from that of CPZ or CEZ. The CPZ or CEZ serum levels in rabbits for the simultaneous adminstration of NB were significantly higher than those for the control experiments, however, the NB serum levels were not greatly affected by CPZ or CEZ.

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