Azalide

Azalides such as azithromycin are a class of macrolide antibiotics that were originally manufactured in response to the poor acid stability exhibited by original macrolides (erythromycin).^[1] Following the clinical overuse of macrolides and azalides, ketolides have been developed to combat surfacing macrolide-azalide resistance among streptococci species.^[2] Azalides have several advantages over erythromycin such as more potent gram negative antimicrobial activity, acid stability, and side effect tolerability.^[3] Although there are few drug interactions with azithromycin, it weakly inhibits the CYP3A4 enzyme.^[2]

Structure

Azalides feature a nitrogen atom in their 15-membered macrolide ring, resulting in improved pharmacokinetic properties and greater stability when compared to earlier-generation macrolides.^[2]^[3] Replacement of the ketone group in traditional macrolides with a tertiary amine group confers greater acid stability.^[3]^[4] See Beckmann rearrangement.

Mechanism of action

Azalides bind to the bacterial 50S ribosomal subunit and inhibit polypeptide elongation by hindering peptidyl transfer RNA translocation.^[3]

Pharmacokinetics

Applicable pharmacokinetic indexes are free azalide AUC₂₄/MIC because of the post antibiotic effect they exhibit, and free azalide concentration/MIC.^[3]^,^[5] Due to their large volume of distribution and lipophilic structure, azalides concentrate effectively in tissue.^[3]

References

^ Thibodeaux, C.J.; Liu, H.-W.; Thorson, J.S. (2007-01-01). "Complementary Routes to Natural Product Glycodiversification: Pathway Engineering and Glycorandomization". Comprehensive Glycoscience. pp. 373–396. doi:10.1016/B978-044451967-2/00040-4. ISBN 9780444519672.
^ ^a ^b ^c Pai, Manjunath P. (2018), "Macrolides, Azalides, and Ketolides", Drug Interactions in Infectious Diseases: Antimicrobial Drug Interactions, Cham: Springer International Publishing, pp. 57–86, doi:10.1007/978-3-319-72416-4_2, ISBN 978-3-319-72415-7, retrieved 2021-04-18
^ ^a ^b ^c ^d ^e ^f So, Wonhee; Nicolau, David P. (2016), "Pharmacodynamics of Macrolides, Azalides, and Ketolides", Methods in Pharmacology and Toxicology, New York, NY: Springer New York, pp. 345–366, doi:10.1007/978-1-4939-3323-5_14, ISBN 978-1-4939-3321-1, retrieved 2021-04-18
^ Mutak, Stjepan (February 2007). "Azalides from Azithromycin to New Azalide Derivatives". The Journal of Antibiotics. 60 (2): 85–122. doi:10.1038/ja.2007.10. ISSN 0021-8820. PMID 17420561.
^ Jacobs, Michael R. (March 2003). "How can we predict bacterial eradication?". International Journal of Infectious Diseases. 7: S13–S20. doi:10.1016/s1201-9712(03)90066-x. ISSN 1201-9712. PMID 12839703.

[1] Thibodeaux, C.J.; Liu, H.-W.; Thorson, J.S. (2007-01-01). "Complementary Routes to Natural Product Glycodiversification: Pathway Engineering and Glycorandomization". Comprehensive Glycoscience. pp. 373–396. doi:10.1016/B978-044451967-2/00040-4. ISBN 9780444519672.

[Pai-2018-2] Pai, Manjunath P. (2018), "Macrolides, Azalides, and Ketolides", Drug Interactions in Infectious Diseases: Antimicrobial Drug Interactions, Cham: Springer International Publishing, pp. 57–86, doi:10.1007/978-3-319-72416-4_2, ISBN 978-3-319-72415-7, retrieved 2021-04-18

[So-2016-3] ^ ^a ^b ^c ^d ^e ^f So, Wonhee; Nicolau, David P. (2016), "Pharmacodynamics of Macrolides, Azalides, and Ketolides", Methods in Pharmacology and Toxicology, New York, NY: Springer New York, pp. 345–366, doi:10.1007/978-1-4939-3323-5_14, ISBN 978-1-4939-3321-1, retrieved 2021-04-18

[4] Mutak, Stjepan (February 2007). "Azalides from Azithromycin to New Azalide Derivatives". The Journal of Antibiotics. 60 (2): 85–122. doi:10.1038/ja.2007.10. ISSN 0021-8820. PMID 17420561.

[5] Jacobs, Michael R. (March 2003). "How can we predict bacterial eradication?". International Journal of Infectious Diseases. 7: S13–S20. doi:10.1016/s1201-9712(03)90066-x. ISSN 1201-9712. PMID 12839703.

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