title: Therapeutic effect of the quinolone prodrug prulifloxacin against experimental urinary tract infections in mice.
abstract: The in vitro antibacterial activity of prulifloxacin (CAS 123447-62-1, NM441), a new quinoline prodrug, against clinical isolates from urinary tract infections was investigated. In addition, it was compared with ofloxacin (CAS 82419-36-1), levofloxacin (CAS 100986-85-4), ciprofloxacin urinary tract infections in mice, as well as its pharmacokinetics. 1. The antibacterial activity of NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2- a]quinoline-3-carboxylic acid), an active metabolite of prulifloxacin, against gram-positive clinical isolates was inferior to that of levofloxacin and tosufloxacin, and equal to that of ofloxacin and ciprofloxacin. Against gram-negative clinical isolates, the activity of NM394 was superior to that of the reference drugs. 2. The therapeutic effect of prulifloxacin on experimental urinary tract infection with Escherichia coli in mice was equal to that of tosufloxacin and ciprofloxacin and superior to that of ofloxacin and levofloxacin. Its therapeutic effect on Pseudomonas aeruginosa infection was equal to that of tosufloxacin and ciprofloxacin, and superior to that of ofloxacin. Against urinary tract infection with olfloxacin-resistant Enterobacter cloacae, prulifloxacin was the most effective of all the drugs tested. 3. The maximal serum concentration of prulifloxacin was slightly higher than that of ciprofloxacin, and the area under the curve (AUC) for prulifloxacin was 1/4 that of ofloxacin, levofloxacin and tosufloxacin. The maximal concentration and AUC of prulifloxacin in lung and kidney were slightly higher than the corresponding values for ciprofloxacin but only 1/2 to 1/4 of the values for ofloxacin, levofloxacin and tosufloxacin. In conclusion, prulifloxacin (NM394) showed potent antibacterial activity against clinical isolates and potent therapeutic efficacy against experimental infection in spite of its lower AUCs compared with the reference drugs. These findings suggest that prulifloxacin may be a useful drug in the treatment of urinary tract infections.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tomii
authors.forename: M
authors.initials: M
authors.lastname: Ozaki
authors.forename: M
authors.initials: M
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Honmura
authors.forename: I
authors.initials: I
authors.lastname: Nishimura
authors.forename: R
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: T
authors.initials: T
authors.lastname: Adachi
authors.forename: Y
authors.initials: Y
authors.lastname: Okawa
authors.forename: T
authors.initials: T
authors.lastname: Nishino
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000892:Anti-Infective Agents, Urinary / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D004148:Dioxolanes / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D024841:Fluoroquinolones; D006207:Half-Life; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D000892:Anti-Infective Agents, Urinary; D004148:Dioxolanes; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; C074191:prulifloxacin