Disease relevance of HSR-903

• These results indicate that clinical studies of HSR-903 against respiratory tract infections may be warranted [1].
• The MICs of HSR-903 for different species of chlamydia were 0.016 to 0.063 microg/ml, which were superior to those of conventional fluoroquinolones [2].
• The MICs at which 90% of the isolates are inhibited (MIC90s) of HSR-903 for Streptococcus pyogenes and penicillin G-susceptible and -resistant Streptococcus pneumoniae (PRSP) were 0.10, 0.05, and 0.05 microg/ml, respectively [3].
• Against Haemophilus influenzae, Moraxella catarrhalis, and Helicobacter pylori, HSR-903 was the most potent of the quinolones tested [3].
• HSR-903 inhibited supercoiling by DNA gyrase from Escherichia coli, but it was much less active against human topoisomerase II [3].

High impact information on HSR-903

• In vitro activity of HSR-903, a new oral quinolone, against bacteria causing respiratory infections [4].
• The therapeutic effect of HSR-903 in experimental mouse Chlamydia psittaci pneumonia was also excellent and almost equal to that of minocycline and superior to that of ofloxacin [2].
• Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease [5].
• When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg [5].
• The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively [5].

Biological context of HSR-903

• Hepatobiliary transport kinetics of HSR-903, a new quinolone antibacterial agent [6].
• The AUC ratios of ELF/plasma and AM/plasma of HSR-903 were 3.03+/-0.54 and 97.5+/-24.2, respectively, notably higher than those of ciprofloxacin (CPFX) [7].

Anatomical context of HSR-903

• Efflux transport of a new quinolone antibacterial agent, HSR-903, across the blood-brain barrier [8].
• Olamufloxacin had equal efficacy for experimental urinary tract infections in mice caused by Pseudomonas aeruginosa [9].
• In conclusion, the low brain distribution of the new quinolone antibacterial agent HSR-903 can be ascribed to multiple efflux mechanisms including P-gp and an unidentified anion-sensitive transporter operating in the brain capillary endothelial cells that constitute the blood-brain barrier [8].
• The initial uptake of HSR-903 by hepatocytes was temperature-dependent, saturable, and stereospecific [6].
• Distribution characteristics of orally administered olamufloxacin, a newly synthesized fluoroquinolone antibacterial, in lung epithelial lining fluid and alveolar macrophage in rats [7].

Associations of HSR-903 with other chemical compounds

• Sparfloxacin was more active, but HSR-903 exhibited the most potent in-vitro activity against the clinical N. gonorrhoeae isolates, including those harbouring quinolone-resistance-associated alterations in GyrA and ParC [10].
• CONCLUSION: Further investigation of the novel quinolones olamufloxacin (HSR 903) and ABT 492 in animal models of plague would seem to be justified [11].
• Furthermore, the permeability of HSR-903 across the cultured AM plasma membrane was 5.5 and 14.5 times greater than those of CPFX and pipemidic acid (PPA), respectively [7].

Gene context of HSR-903

• These observations support the idea that P-gp participates in HSR-903 efflux from the brain [8].
• These results demonstrate that HSR-903 is actively excreted into bile via the canalicular multispecific organic anion transporter, which is deficient in EHBR [6].

Analytical, diagnostic and therapeutic context of HSR-903

• The extraction ratio of HSR-903 in isolated lung perfusion was temperature dependent and saturable [12].
• The lung concentration of unchanged HSR-903 was about nine times higher than that in plasma after oral administration (5 mg/kg) in rats [12].

References