In Vitro and In Vivo Antibacterial Activities of the Tricyclic Ketolide TE-802 and Its Analogs

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-posit...

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Bibliographic Details
Published in:Journal of antibiotics 2004/08/25, Vol.57(8), pp.518-527
Main Authors: ONO, TAKEO, KASHIMURA, MASATO, SUZUKI, KEIKO, OYAUCHI, RIKA, MIYACHI, JUNKO, IKUTA, HIROSHI, KAWAUCHI, HIROYUKI, AKASHI, TOSHI, ASAKA, TOSHIFUMI, MORIMOTO, SHIGEO
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - pharmacokinetics
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Humans
Hydrogen-Ion Concentration
Ketolides - pharmacokinetics
Ketolides - pharmacology
Ketolides - therapeutic use
Male
Mice
Mice, Inbred ICR
Microbial Sensitivity Tests
Mycoplasma pneumoniae
Respiratory Tract Infections - drug therapy
Staphylococcus aureus
Streptococcus pneumoniae
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Summary: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 Gramnegative 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, po) of TE-802 in mice were equal to that of CAM, but the plasma area under the concentration-time curve (AUC24 hours) was 4.7 times that for CAM. The plasma Cmax (po) value for TE-802 in monkey was equal to that of CAM, whereas the AUC8 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.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.57.518