title: Comparison of antimycobacterial activity of grepafloxacin against Mycobacterium avium with that of levofloxacin: accumulation of grepafloxacin in human macrophages.
abstract: The bactericidal activity of two new quinolones, grepafloxacin and levofloxacin, against five strains of Mycobacterium avium was investigated in vitro. The minimum inhibitory concentrations (MICs) of these two quinolones, determined by the broth microdilution method, were comparable for all strains tested. In contrast, grepafloxacin suppressed the intracellular growth of all the strains in monocyte-derived macrophages more strongly than levofloxacin, when the cells infected with these strains were incubated for 7 days in the presence of various concentrations of the two new quinolones. To find the reason for the strengthened intracellular killing activity of grepafloxacin, we determined the ratio of the concentration of the new quinolones in the cells to that in the medium (C/M concentration ratio). The C/M concentration ratio of grepafloxacin was increased to 34.7 by 7 days, whereas that of levofloxacin at 7 days was only 12.3. These data suggested that a higher level of intraphagocytic accumulation of grepafloxacin endows it with greater mycobactericidal activity.
authors.affiliation: Department of Drug Metabolism, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirota
authors.forename: T
authors.initials: T
authors.lastname: Totsu
authors.forename: F
authors.initials: F
authors.lastname: Adachi
authors.forename: K
authors.initials: K
authors.lastname: Kamikawa
authors.forename: J
authors.initials: J
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Kanegasaki
authors.forename: K
authors.initials: K
authors.lastname: Nakata
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002478:Cells, Cultured / Q000378:metabolism / Q000382:microbiology; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D006801:Humans; D064704:Levofloxacin; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D009162:Mycobacterium avium / Q000187:drug effects* / Q000254:growth & development; D015242:Ofloxacin / Q000378:metabolism / Q000494:pharmacology*; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D003470:Culture Media; D024841:Fluoroquinolones; D010879:Piperazines; D064704:Levofloxacin; D015242:Ofloxacin; C075375:grepafloxacin