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Chemical Compound Review

Restanza     (1S,2R,5R,7R,8R,9R,11R,13R,14R )-8-[(2S,3R...

Synonyms: Cethromycin, AC1NQZEX, ABT-773, Abbott-195773, CHEMBL133924, ...
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Disease relevance of ABT-773


High impact information on ABT-773

  • METHODS: Healthy volunteers given 3 different oral dose levels of ABT-773 were genotyped at 2 common CYP3A5 and 7 common MDR-1 polymorphisms [4].
  • ABT-773 plasma levels did not trend with MDR-1 genotypes [4].
  • The serum protein binding levels of cethromycin were 94.8 and 88.5% after doses of 12.5 and 25 mg/kg, respectively [2].
  • The U2609C mutation, which renders E. coli resistant to the previously studied ketolides telithromycin and cethromycin, barely affected cell susceptibility to the bridged macrolides used in this study [5].
  • In this mouse model, treatment with cethromycin significantly reduced M. pneumoniae culture titers in BAL samples, cytokine and chemokine concentrations in BAL samples, histologic inflammation in the lungs, and disease severity as defined by AO and AHR [6].

Chemical compound and disease context of ABT-773


Biological context of ABT-773

  • CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels [4].
  • Steady-state plasma and intrapulmonary pharmacokinetics and pharmacodynamics of cethromycin [12].
  • We also showed that ABT-773 (i) accumulated in macrolide-sensitive S. pneumoniae at a higher rate than erythromycin, (ii) was able to bind with methylated ribosomes, though at lower affinities than with wild-type ribosomes, and (iii) accumulated in S. pneumoniae strains with the efflux-resistant phenotype [13].
  • We concluded that the C(max)/MIC(90) ratios, AUC/MIC(90) ratios, %T > MIC(90) values, and extended plasma and intrapulmonary half-lives provide a pharmacokinetic rationale for once-daily administration and are favorable for the treatment of cethromycin-susceptible pulmonary infections [12].
  • Sucralfate had no impact on the bioavailability of ABT-773 [14].

Anatomical context of ABT-773


Associations of ABT-773 with other chemical compounds


Gene context of ABT-773

  • Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s were 0.016 to 0.03 and 0.125 microgram/ml, respectively [18].
  • ABT-773 showed excellent activity against macrolide, azalide, lincosamide (MAL) inducible S. aureus producers but was inactive against constitutive producers [19].

Analytical, diagnostic and therapeutic context of ABT-773


  1. Recent developments on ketolides and macrolides. Wu, Y.J., Su, W.G. Current medicinal chemistry. (2001) [Pubmed]
  2. Efficacy of cethromycin, a new ketolide, against Streptococcus pneumoniae susceptible or resistant to erythromycin in a murine pneumonia model. Azoulay-Dupuis, E., Mohler, J., Bédos, J.P., Barau, C., Fantin, B. Antimicrob. Agents Chemother. (2006) [Pubmed]
  3. Efficacies of ABT-773, a new ketolide, against experimental bacterial infections. Mitten, M.J., Meulbroek, J., Nukkala, M., Paige, L., Jarvis, K., Oleksijew, A., Tovcimak, A., Hernandez, L., Alder, J.D., Ewing, P., Or, Y.S., Ma, Z., Nilius, A.M., Mollison, K., Flamm, R.K. Antimicrob. Agents Chemother. (2001) [Pubmed]
  4. CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels. Katz, D.A., Grimm, D.R., Cassar, S.C., Gentile, M.C., Ye, X., Rieser, M.J., Gordon, E.F., Polzin, J.E., Gustavson, L.E., Driscoll, R.M., O'dea, R.F., Williams, L.A., Bukofzer, S. Clin. Pharmacol. Ther. (2004) [Pubmed]
  5. Binding site of the bridged macrolides in the Escherichia coli ribosome. Xiong, L., Korkhin, Y., Mankin, A.S. Antimicrob. Agents Chemother. (2005) [Pubmed]
  6. Impact of cethromycin (ABT-773) therapy on microbiological, histologic, immunologic, and respiratory indices in a murine model of Mycoplasma pneumoniae lower respiratory infection. Ríos, A.M., Mejías, A., Chávez-Bueno, S., Fonseca-Aten, M., Katz, K., Hatfield, J., Gómez, A.M., Jafri, H.S., McCracken, G.H., Ramilo, O., Hardy, R.D. Antimicrob. Agents Chemother. (2004) [Pubmed]
  7. In vitro activity of the ketolide ABT-773. Barry, A.L., Fuchs, P.C., Brown, S.D. Antimicrob. Agents Chemother. (2001) [Pubmed]
  8. In vitro activity of ABT-773 against Legionella pneumophila, its pharmacokinetics in guinea pigs, and its use to treat guinea pigs with L. pneumophila pneumonia. Edelstein, P.H., Higa, F., Edelstein, M.A. Antimicrob. Agents Chemother. (2001) [Pubmed]
  9. In vivo efficacy of the ketolide ABT-773 (cethromycin) against enterococci in a mouse peritonitis model. Pai, S.R., Singh, K.V., Murray, B.E. Antimicrob. Agents Chemother. (2003) [Pubmed]
  10. In vitro activities of a new ketolide, ABT-773, against multidrug-resistant gram-positive cocci. Singh, K.V., Malathum, K., Murray, B.E. Antimicrob. Agents Chemother. (2001) [Pubmed]
  11. In vitro bactericidal activity of ABT-773 and amoxicillin against erythromycin-susceptible and -resistant strains of Streptococcus pyogenes. Pendland, S.L., Neuhauser, M.M., Prause, J.L. J. Antimicrob. Chemother. (2002) [Pubmed]
  12. Steady-state plasma and intrapulmonary pharmacokinetics and pharmacodynamics of cethromycin. Conte, J.E., Golden, J.A., Kipps, J., Zurlinden, E. Antimicrob. Agents Chemother. (2004) [Pubmed]
  13. Studies of the novel ketolide ABT-773: transport, binding to ribosomes, and inhibition of protein synthesis in Streptococcus pneumoniae. Capobianco, J.O., Cao, Z., Shortridge, V.D., Ma, Z., Flamm, R.K., Zhong, P. Antimicrob. Agents Chemother. (2000) [Pubmed]
  14. ABT-773: pharmacokinetics and interactions with ranitidine and sucralfate. Pletz, M.W., Preechachatchaval, V., Bulitta, J., Allewelt, M., Burkhardt, O., Lode, H. Antimicrob. Agents Chemother. (2003) [Pubmed]
  15. Interaction of the new ketolide ABT-773 (cethromycin) with human polymorphonuclear neutrophils and the phagocytic cell line PLB-985 in vitro. Labro, M.T., Abdelghaffar, H., Babin-Chevaye, C. Antimicrob. Agents Chemother. (2004) [Pubmed]
  16. Comparison of in vitro activities of ABT-773 and telithromycin against macrolide-susceptible and -resistant streptococci and staphylococci. Shortridge, V.D., Zhong, P., Cao, Z., Beyer, J.M., Almer, L.S., Ramer, N.C., Doktor, S.Z., Flamm, R.K. Antimicrob. Agents Chemother. (2002) [Pubmed]
  17. In vitro bactericidal activity and post-antibiotic effect of ABT-773 versus co-amoxiclav against anaerobes. Pendland, S.L., Neuhauser, M.M., Prause, J.L. J. Antimicrob. Chemother. (2002) [Pubmed]
  18. Antipneumococcal activity of ABT-773 compared to those of 10 other agents. Davies, T.A., Ednie, L.M., Hoellman, D.M., Pankuch, G.A., Jacobs, M.R., Appelbaum, P.C. Antimicrob. Agents Chemother. (2000) [Pubmed]
  19. In vitro activity of the new ketolide ABT-773 against community acquired respiratory tract isolates and Viridans Streptococci. Casellas, J.M., Tomé, G., Visser, M., Gliosca, L. Diagn. Microbiol. Infect. Dis. (2002) [Pubmed]
  20. Pharmacokinetics of ABT-773, a new semi-synthetic ketolide in neutropenic lung-infected mice: a population approach. Xuan, D., Ye, M., Kim, M., Nightingale, C.H., Nicolau, D.P. J. Pharm. Pharmacol. (2002) [Pubmed]
  21. Ribosome affinity and the prolonged molecular postantibiotic effect of cethromycin (ABT-773) in Haemophilus influenzae. Cao, Z., Zhong, P., Ruan, X., Merta, P., Capobianco, J.O., Flamm, R.K., Nilius, A.M. Int. J. Antimicrob. Agents (2004) [Pubmed]
  22. A high-performance liquid chromatographic-tandem mass spectrometric method for the determination of cethromycin (ABT-773) in human plasma, bronchoalveolar lavage fluid, and alveolar cells. Ren, Q., Conte, J.E., Zurlinden, E., Lin, E.T. Journal of chromatographic science. (2003) [Pubmed]
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