Comparative serum levels and protective activity of parenterally administered cephalosporins in experimental animals

Six cephalosporin antibiotics were administered subcutaneously to mice at a level of 20 mg/kg. The serum levels of each were determined at five time intervals ranging from 5 to 120 min after dosing. Urinary recovery and the presence of active metabolites in mouse urine were determined. The peak serum levels and serum half-lives in mice were found to be positively correlated with the mean effective dose values obtained after lethal challenge with Escherichia coli. The administration of cefazolin and cephanone resulted in the highest serum level and the best protection. Good protection was obtained with cephaloridine despite somewhat lower serum levels. The cephalosporins with the acetoxy side chain (cephalothin, cephapirin, and cephacetrile) showed lower serum levels and the poorest protection. Cefazolin, cephaloridine, and cephalothin serum levels were also determined in dogs, squirrel monkeys, and rabbits. A mixed response was obtained in these species, with cefazolin peak serum levels being highest in rabbits and cephaloridine peak highest in dogs.