title: Uptake and intracellular activity of AM-1155 in phagocytic cells.
abstract: The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated. AM-1155 penetrated phagocytic cells rapidly and reversibly, although the penetration process was not affected by metabolic inhibitors such as sodium fluoride, cyanide m-chlorophenylhydrazone, or ouabain or by nucleoside transport system inhibitors such as adenosine. The intracellular concentration-to-extracellular concentration ratio of AM-1155 in both cell types of phagocytes ranged from 5 to 7. These ratios were almost equal to those for sparfloxacin. The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration. AM-1155 at a concentration of 1 microgram/ml reduced the number of viable cells of S. aureus ingested by more than 90%. The intracellular activity of AM-1155 was more potent than those of sparfloxacin, ofloxacin, ciprofloxacin, flomoxef, and erythromycin. These results suggest that the potent intracellular activity of AM-1155 might mainly be due to the high intracellular concentration and its potent in vitro activity.
authors.affiliation: Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Kusajima
authors.forename: M
authors.initials: M
authors.lastname: Hosaka
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: Y
authors.initials: Y
authors.lastname: Oomori
authors.forename: H
authors.initials: H
authors.lastname: Shinoda
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; D000077734:Gatifloxacin