Azalide

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Azithromycin Azithromycin structure.svg
Azithromycin

Azalides are a class of macrolide antibiotics that were originally manufactured in response to the poor acid stability exhibited by original macrolides such as erythromycin. [1] Examples of azalides include azithromycin, which is used in humans, while tulathromycin and gamithromycin are used in veterinary medicine. 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]

Contents

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

  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.
  2. 1 2 3 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
  3. 1 2 3 4 5 6 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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