Serum protein binding of a new oral cephalosporin, CL 284,635, in various species.
CL 284,635 is a new third generation oral cephalosporin. Its serum protein binding was investigated in the human, monkey, dog, rat, and rabbit. This study was performed by using an equilibrium dialysis and ultrafiltration method, using radiolabeled and cold CL 284,635. In humans, CL 284,635 was found to have a mean free fraction [fu = concentration of unbound (free) drug divided by total concentration of unbound plus bound to serum proteins] of 31.3 +/- 3.3% with no serum concentration dependency in a range of 0.5 to 26 micrograms/ml. The drug was mainly bound to albumin. In rabbits and monkeys the protein binding profile of CL 284,635 was found to be 36.1 +/- 2.3% and 33.9 +/- 1.5% with no serum concentration dependency. In rats and dogs a non-concentration-dependent fu was observed at serum concentrations ranging from 0.5 to 30 micrograms/ml. A gradual increase in fu values was observed at higher serum concentrations of CL 284,635. Overall, the protein binding profile of CL 284,635 was found to be different in the five investigated species. The protein binding of CL 284,635 in monkeys and rabbits was most similar to that in humans. These species differences in protein binding may have an impact on the disposition of the drug in different species.
Bialer
M
M
Tonelli
A P
AP
Kantrowitz
J D
JD
Yacobi
A
A
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000378:metabolism; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D013045:Species Specificity
D001798:Blood Proteins; D012709:Serum Albumin; D020682:Cefixime; D002439:Cefotaxime