title: In vivo antibacterial activity of FK041, a new orally active cephalosporin.
abstract: The therapeutic activities of orally administered FK041 were evaluated in mouse models of systemic and local infections with a variety of bacteria and were compared with those of cefdinir (CFDN) and cefditoren pivoxil (CDTR-PI). FK041 exhibited potent therapeutic activity against lethal systemic infections induced by intraperitoneally inoculated Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae with 50% effective doses (ED50) in the range of 0.20 to 0.36 mg/kg and was more active than CFDN and CDTR-PI. This result correlated well with its in vitro activity. The therapeutic effects of FK041 and reference drugs on murine local infections were evaluated in an in vivo pharmacokinetic model simulating human plasma concentrations for oral administration of 50 mg, 100 mg, and 200 mg. Against murine subcutaneous abscess induced by S. aureus, FK041 was as effective as CFDN and significantly more effective than CDTR-PI in reducing the number of recoverable viable bacteria in the skin at the infection sites. The efficacy of FK041 against murine pneumonia with H. influenzae was comparable to that of CDTR-PI and was superior to that of CFDN in reducing viable bacteria activity in the lungs. These results strongly suggest that FK041 has potential for clinical use against various bacterial infections.
authors.affiliation: Research Planning, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tawara
authors.forename: K
authors.initials: K
authors.lastname: Hatano
authors.forename: Y
authors.initials: Y
authors.lastname: Wakai
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: F
authors.initials: F
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Kuwahara
mesh_terms: D000818:Animals; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D001922:Brain Abscess / Q000188:drug therapy / Q000382:microbiology; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006192:Haemophilus Infections / Q000188:drug therapy; D006193:Haemophilus influenzae; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013203:Staphylococcal Infections / Q000188:drug therapy
chemical_list: D002511:Cephalosporins; C114137:FK 041