gemifloxacin and Inflammation

The pharmacokinetics and tissue penetration of gemifloxacin were determined during a 24 h period following oral administration of a single 320 mg dose to each of 10 healthy male volunteers. Concentrations of the drug in plasma, inflammatory blister fluid and urine were determined using a microbial assay. A peak plasma concentration (mean +/- S.D.) of 2.33 +/- 0.5 mg/L was reached at 1.20 +/- 0.4 h. Mean penetration into inflammatory fluid was 61.19 +/- 10.4%. A peak concentration of 0.74 +/- 0.3 mg/L was reached in the inflammatory fluid at a mean time of 3.40 +/- 1.7 h. The mean elimination half-life from serum and inflammatory fluid was 5.94 +/- 0.4 and 6.27 +/- 2.4 h, respectively. Urinary excretion of the drug at 24 h post-dose was 36.11% of the total given. These results demonstrate that gemifloxacin penetrates into the site of inflammation and reaches sufficient concentrations to inhibit many pathogens.

Topics: Administration, Oral; Adult; Anti-Infective Agents; Blister; Data Interpretation, Statistical; Fluoroquinolones; Gemifloxacin; Half-Life; Humans; Inflammation; Male; Naphthyridines; Skin

Gemifloxacin (GMF) is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT). In addition, GMF suppresses the activation of NF- κ B and cell migration and invasion induced by TNF- α and inhibits the TAK1/TAB2 interaction, resulting in decreased I κ B phosphorylation and NF- κ B nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

Topics: Anti-Infective Agents; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cell Nucleus; Colonic Neoplasms; Drug Screening Assays, Antitumor; Epithelial-Mesenchymal Transition; Fluoroquinolones; Gemifloxacin; Humans; Inflammation; Naphthyridines; Neoplasm Invasiveness; NF-kappa B; Protein Transport; Snail Family Transcription Factors; Transcription Factors; Tumor Necrosis Factor-alpha