Laboratory evaluation of FR10612, a new oral cephalosporin derivative.

FR10612, like cephalexin, is a broad-spectrum oral cephalosporin derivative. The antimicrobial activity of FR10612 against clinical isolates was similar to cephalexin; however, at a low inoculum size its activity was greater than cephalexin against Klebsiella pneumonia and Proteus mirabilis strains. Like cephalexin, the in vitro bactericidal activity of FR10612 was more influenced by the duration of contact with the test organism than by drug concentration. The bactericidal activity of FR10612 against E. coli 317 was greater than that of cephalexin in an in vitro model system which simulated the serum levels of FR10612 and cephalexin achieved in healthy volunteers after a single oral dose. The protein binding of FR10612 to human and animal serum was extremely low. FR10612 was resistant to β-lactamases from gram-negative bacilli. It showed resistance similar to cephalexin, but was more resistant to β-lactamases than were cephaloridine, cephalothin and cefazolin. The protective effect of FR10612 in mice infected with various pathogens was greater than cephalexin. The serum levels of FR10612 in rats were higher and more prolonged than those of cephalexin. Tissue levels of FR10612 in rats also persisted for a long time period reflecting the serum levels. In healthy volunteers, rabbits and monkeys the serum levels of FR10612 were initially lower than those of cephalexin but persisted for a longer time period. The total 24-hour urinary excretion of FR10612 in healthy volunteers after oral administration was almost the same as that of cephalexin, but the excretion rate of FR10612 was slower, and the urinary levels were more persistent than those of cephalexin.