The antibacterial activity of
OPC-17116, a new
fluoroquinolone antibacterial agent, against important pathogens that cause
respiratory tract infections was evaluated in vitro and in vivo and compared with those of
ciprofloxacin,
ofloxacin, and
norfloxacin. The pharmacokinetic profiles of
OPC-17116 were studied in both mice and rats given the
drug orally at doses of 50 and 40 mg/kg of
body weight, respectively.
OPC-17116 showed a high degree of distribution in the lung tissues of both species, with maximum concentrations of 29.6 and 32.0 micrograms/g, respectively. Furthermore, the
drug concentrations in lung tissue were about 10 to 15 times greater than the concentrations in plasma.
OPC-17116 showed potent antibacterial activity against such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis. The MICs of this compound for 90% of these organisms except methicillin-resistant S. aureus and P. aeruginosa ranged from < or = 0.006 to 0.78 microgram/ml. The in vitro antibacterial activity of
OPC-17116 was reflected by the efficacy of a single oral dose against systemic
bacterial infections in mice.
OPC-17116 showed a superior effect against gram-positive bacteria, H. influenzae, and M. catarrhalis. In comparison with the other reference compounds, the efficacy of
OPC-17116 was less than that of
ciprofloxacin against K. pneumoniae and P. aeruginosa.
OPC-17116 showed a greater
therapeutic effect than the other drugs against experimental acute
pneumonia caused by these organisms in mice or rats. This excellent
therapeutic effect against
respiratory tract infections may be a result of its high level of distribution in lung tissue.