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Evaluation of OPC-17116 against important pathogens that cause respiratory tract infections
1Second Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Abstract:
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.
Insights
OPC-17116, a new fluoroquinolone, demonstrates potent antibacterial activity against respiratory pathogens and superior lung tissue distribution. This new agent shows promising therapeutic effects for respiratory tract infections.
Area of Science:
- Pharmacology
- Microbiology
- Infectious Diseases
Background:
- Respiratory tract infections (RTIs) pose a significant global health challenge.
- Novel antibacterial agents are crucial to combat rising antimicrobial resistance.
- Fluoroquinolones are a key class of antibiotics used to treat bacterial infections.
Purpose of the Study:
- To evaluate the in vitro and in vivo antibacterial activity of OPC-17116 against key respiratory pathogens.
- To compare OPC-17116 with established fluoroquinolones (ciprofloxacin, ofloxacin, norfloxacin).
- To investigate the pharmacokinetic profile of OPC-17116, particularly its distribution in lung tissue.
Main Methods:
- In vitro susceptibility testing (MIC determination) against various bacterial pathogens.
- In vivo efficacy studies in mouse models of systemic infection.
- Pharmacokinetic studies in mice and rats to assess drug distribution, especially in lung tissue.
- Experimental acute pneumonia models in mice and rats.
Main Results:
- OPC-17116 exhibited potent activity against Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis.
- The drug showed high lung tissue distribution (29.6-32.0 µg/g) in mice and rats, with concentrations 10-15 times higher than in plasma.
- OPC-17116 demonstrated superior efficacy against gram-positive bacteria, H. influenzae, and M. catarrhalis in vivo.
- While less effective than ciprofloxacin against K. pneumoniae and P. aeruginosa, OPC-17116 showed a greater therapeutic effect in experimental pneumonia models.
Conclusions:
- OPC-17116 possesses significant in vitro and in vivo antibacterial activity relevant to RTIs.
- Its excellent lung tissue penetration is a key factor contributing to its therapeutic efficacy.
- OPC-17116 represents a promising candidate for treating respiratory tract infections, potentially due to its favorable pharmacokinetic and pharmacodynamic properties.