• Journal of Pharmaceutical Investigation
• /
• v.39 no.6
• /
• pp.431-435
• /
• 2009

The comparative superior in vitro activity of DW-224a was supported by the downward MIC distribution due to the weakened influence of alterations within target enzymes in ciprofloxacin-resistant Staphylococcus aureus. The MI$C_{50}$ for DW-224a was 4 $\mu$g/mL, similar to that of gemifloxacin, 8-fold less than that of sparfloxacin and 16-over-fold less than that of ciprofloxacin. We constructed combinations of amino acid changes, located at codon 80, 83 or 84 within GrlA and 84, 85 or 88 within GyrA, which were associated with MIC increase. The amino acid changes were less influential to the MIC of DW-224a compared to those of other fluoroquinolones, and it was verified from the requirement of a total of two GrlA- and two GyrA-alterations to reach the MIC of DW-224a over 32 $\mu$g/mL.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.10b
• /
• pp.170-170
• /
• 2003

DW -224a is a fluoroquinolone antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative bacteria. In order to clarify toxicokinetic profile of DW-224a, a 4-week repeated dose oral toxicokinetic study (dose level: 0, 63, 250, 1000 mg/kg) was conducted in groups of Sprague-Dawley rats.(omitted)

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.193-193
• /
• 2002

The subacute toxicities and toxicokinetics of a new fluoroquinolone antibiotics, DW-224a, were evaluated after single (at the 1st day) and 4-week (at the 28th day) oral administration of the drug, in doses of 0 (to serve as a control), 10, 30 and 90 mg/kg/day, to male and female dogs (n = 3 for male and female dogs for each dose).(omitted)

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2003.10a
• /
• pp.170-170
• /
• 2003

• Proceedings of the Korea Environmental Mutagen Society Conference
• /
• 2002.11a
• /
• pp.193-193
• /
• 2002

• YAKHAK HOEJI
• /
• v.52 no.3
• /
• pp.219-224
• /
• 2008

Clinically isolated methicillin-resistant Staphylococcus aureus strains were exposed to subinhibitory concentration of DW286, DW-224a, gemifloxacin, trovafloxacin, sparfloxacin and ciprofloxacin during 26- to 39-days period. Subculturing led to resistance development, and most of the selected mutants were above susceptible breakpoints. Selected mutants had broad cross resistance to other quinolone antibiotics and only one mutant was completely susceptible to all fluoroquinolones. Twenty five among 42 mutants revealed mutations on DNA gyrase and topoisomerase IV by sequencing. Also 16 mutants had fluoroquinolones MICs that were 4-32 times lower in the presence of reserpine. In conclusion, alterations in DNA gyrase or topoisomerase IV and action of efflux pumping out system are the resistance mechanisms of DW-224a.