Comparative Serum Levels and Protective Activity of Parenterally Administered Cephalosporins in Experimental Animals

Abstract

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.

Clinical Pharmacology of Cefazolin in Calves

“…Several possible reasons can be given for these differences in the kinetic properties of cefazolin from those of the other p-lactam antibiotics investigated in calves. In the first place, the elimination t % of cefazolin after i. v. injection in man is 104 min but in the horse (13) it is considerably shorter (38 min), as in calves (Table 2), and still shorter (30min) in the dog (7). Secondly, the total body clearance (Clb) of cefazolin in man ranges between 0.74 and 0.90 ml/min/kg (10); in the dog it averages 10.4ml/min/kg and in the horse it averages 5.51 ml/min/kg, just as in calves (Table 2).…”

“…Pharmacokinetic data on cefazolin are available for mice (5, 7), rats (8, 1 I), rabbits (5, 7), dogs (5,8), horses (13) and man (10,12,20). Despite the potential clinical utility of cefazolin in calves, records of pharmacokinetic or bioavailability data were not found for these animals in the literature.…”

<i>In vitr</i><i>o</i> and <i>in vivo</i> Comparative Evaluations of Injectable Cephalosporin Derivatives and Ampicillin

“…The ED50 values of cefazolin and cephaloridine for gram-negative organisms were far low er than those of the other 3 cephalosporins. The reason why the in vivo activity of cefazolin and cephaloridine was higher than that of the other cephalosporins is explainable by the higher concentrations of cefazolin and cephaloridine in the serum [4], urine and tissues [5]. In this case, it is necessary to consider that cephalothin, cephapirin and cephacetrile are partially converted into their respective desacetvl forms [6,7].…”