title: In vitro and in vivo antibacterial activities of the tricyclic ketolide TE-802 and its analogs.
abstract: The in vitro and in vivo antibacterial activities of tricyclic ketolides (TKs: TE-802, TE-806, TE-935, TE-943) have been compared with those of clarithromycin (CAM), azithromycin (AZM) and rokitamycin (RKM). TKs were active against not only erythromycin (EM)-susceptible organisms; aerobic gram-positive bacteria, some gram-negative bacteria, anaerobic bacteria and Mycoplasma pneumoniae, but also EM-resistant Staphylococcus aureus (inducible macrolide-resistant strains) as well as EM-resistant Streptococcus pneumoniae (efflux-resistant strains). The therapeutic efficacies of TKs against systemic infections and respiratory tract infection (RTI) caused by gram-positive bacteria in mice are superior to those of CAM and AZM. The peak plasma levels (Cmax, p.o.) of TE-802 in mice were equal to that of CAM, but the plasma area under the concentration-time curve (AUC(24 hours)) was 4.7 times that for CAM. The plasma Cmax (p.o.) value for TE-802 in monkey was equal to that of CAM, whereas the AUC(8 hours) value was three-fourths that of CAM. The pharmacokinetics of TE-802 are similar to those of AZM in mice and monkeys, suggesting the potential for once-daily administration in humans.
authors.affiliation: Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama, 331-9530, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Ono
authors.forename: Masato
authors.initials: M
authors.lastname: Kashimura
authors.forename: Keiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Rika
authors.initials: R
authors.lastname: Oyauchi
authors.forename: Junko
authors.initials: J
authors.lastname: Miyachi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikuta
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawauchi
authors.forename: Toshi
authors.initials: T
authors.lastname: Akashi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Asaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D048628:Ketolides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D012141:Respiratory Tract Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; C437368:TE-802