The in vitro antibacterial activity of
prulifloxacin (CAS 123447-62-1, NM441), a new
quinoline prodrug, against clinical isolates from
urinary tract infections was investigated. In addition, it was compared with
ofloxacin (CAS 82419-36-1),
levofloxacin (CAS 100986-85-4),
ciprofloxacin urinary tract infections in mice, as well as its pharmacokinetics. 1. The antibacterial activity of
NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2- a]
quinoline-3-
carboxylic acid), an active metabolite of
prulifloxacin, against gram-positive clinical isolates was inferior to that of
levofloxacin and
tosufloxacin, and equal to that of
ofloxacin and
ciprofloxacin. Against gram-negative clinical isolates, the activity of
NM394 was superior to that of the reference drugs. 2. The
therapeutic effect of
prulifloxacin on experimental
urinary tract infection with Escherichia coli in mice was equal to that of
tosufloxacin and
ciprofloxacin and superior to that of
ofloxacin and
levofloxacin. Its
therapeutic effect on
Pseudomonas aeruginosa infection was equal to that of
tosufloxacin and
ciprofloxacin, and superior to that of
ofloxacin. Against
urinary tract infection with olfloxacin-resistant Enterobacter cloacae,
prulifloxacin was the most effective of all the drugs tested. 3. The maximal serum concentration of
prulifloxacin was slightly higher than that of
ciprofloxacin, and the area under the curve (AUC) for
prulifloxacin was 1/4 that of
ofloxacin,
levofloxacin and
tosufloxacin. The maximal concentration and AUC of
prulifloxacin in lung and kidney were slightly higher than the corresponding values for
ciprofloxacin but only 1/2 to 1/4 of the values for
ofloxacin,
levofloxacin and
tosufloxacin. In conclusion,
prulifloxacin (
NM394) showed potent antibacterial activity against clinical isolates and potent therapeutic efficacy against experimental
infection in spite of its lower AUCs compared with the reference drugs. These findings suggest that
prulifloxacin may be a useful
drug in the treatment of
urinary tract infections.