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Biomedical subjects

Toshifumi Asaka

Publications and source records attributed to Toshifumi Asaka.

4 recordsLinked to original sources
PubMed2004

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-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.

Animals↗
PubMed2003

Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetylerythromycin A derivatives.

A novel series of acylides, 3-O-(aryl)acetylerythromycin A derivatives, were synthesized and evaluated. These compounds have significant potent antibacterial activity against not only Gram-positive pathogens, including inducibly macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens, such as H. influenzae. 6,9:11,12-dicarbonate acylide 47 (FMA0122) was twice as active against H. influenzae than azithromycin, whereas it showed only moderate in vivo efficacy in mouse protection tests. However, the 11,12-carbamate acylide 19 (TEA0929), which showed potent antibacterial activity against almost all of the main causative pathogens of community-acquired pneumonia tested, exhibited excellent in vivo efficacy comparable to those of second-generation macrolides.

Administration, Oral↗
PubMed2003

Recent developments in macrolide antimicrobial research.

Clarithromycin and azithromycin, which are more acid-stable than erythromycin A (EM), have been widely prescribed for the treatment of respiratory tract infections because of their high efficacy and safety. However, these macrolide antibiotics are only weakly active against pathogens with an efflux gene (mef) and are inactive against pathogens with a methyltransferase-inducible gene (erm) and constitutively resistant organisms. To address the drug resistance issue, tremendous efforts have been devoted to the modification of the macrolide structure. As a consequence, several types of decladinosyl derivatives, such as ketolide and acylides, have been recognized to be effective against mef-type resistant streptococci and methylase-inducible staphylococci. It has also been recognized that derivatives containing certain 11-, 6- or 4 -tethered aryl substituents, such as telithromycin (HMR 3647), cethromycin (ABT-773) and CP-544372, are effective against erm(B)-type resistant streptococci. Telithromycin was recently approved in several European countries for the treatment of respiratory tract infections and cethromycin is now in the final stage of clinical study. Macrolide antibiotics have been modified to address the issues of acid-instability and inactivity against resistant strains. In this review, we will summarize the progress in the macrolide research area and discuss the desirable features of the next generation macrolide antibiotics.

Anti-Bacterial Agents↗