In vivo efficacy of cefcanel daloxate in comparison with cefaclor

Cefcanel daloxate is a new prodrug cephalosporin for oral use, with cefcanel as the antibacterially active principle. The in vivo efficacy of this prodrug in comparison with cefaclor was assessed in a localized thigh infection model in mice. Mice were infected intramuscularly in the thigh and treated orally with cefcanel daloxate or cefaclor with three doses given 70 min apart. One strain each of S. aureus, Escherichia coli and Klebsiella pneumoniae was used as test organism. The first dose was given 60 min after staphylococcal infection or 15 min after infection with the Gram-negative strains. The doses given were 0.1 or 0.5 mmol/kg body weight, respectively. The animals were killed at predetermined times, the thigh was excised and homogenized and a count of viable bacteria was made. Decrease in bacterial numbers was used as a measure of the efficacy. The plasma and muscle concentrations of the two investigated drugs were also determined. Both drugs caused a reduction in viable count by approx. 90% for all test organisms, while in the untreated animals the number of bacteria increased 4 to 10 times within 6 hours after challenge. The plasma and tissue peak levels of cefcanel following administration of the daloxate were lower than those for cefaclor but cefcanel displayed a longer half-life.