Probenecid and the antibacterial activity of cephradine in vivo.

The influence of probenecid on the concentrations in blood and antibacterial efficacy of cephradine was studied in experimentally infected mice. An infection was induced by injection of 5 X 10(6) Escherichia coli into the thighs of irradiated, granulocytopenic mice. Probenecid was given 1 hr later, just before the administration of cephradine. The control animals received only the vehicle. Concentrations of cephradine in blood were determined for 2 hr; the antibacterial activity was estimated from bacterial counts made in the homogenized individual thighs. The blood concentrations of cephradine were 1.77 times higher in the probenecid-treated animals than in the controls. The potency ratio for doses was 2.41, the potency ratio for the areas under the drug concentration in blood vs. time curves was 1.34, and that for the peak blood concentrations was 1.43.