Cefazolin and cephradine: relationship between serum concentrations and tissue contents in mice

The relationship between serum concentrations and tissue levels of various doses of cefazolin and cephradine was determined in experimentally infected mice. An infection was induced by injection of 5 X 10(6) Escherichia coli into the right hind leg, antibiotics were administered 1 h later. At 15-minute intervals mice were killed by exsanguination after a blood sample was taken, and the infected thigh was taken out and homogenized. The total amount of antibiotic per gram thigh muscle tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between blood concentrations and total tissue contents it may be concluded that the thigh was easily accessible for both cephalosporins. The ratio between the total tissue content and the free serum concentrations was the same for both antibiotics despite the difference in protein binding between cefazolin and cephradine in mouse serum. This implies that the discrepancy between the relative antibacterial activity of the cephalosporins in vitro and in vivo found in earlier experiments cannot be explained by differences in accessibility of the tissue.