Chemistry: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 CYP4A4 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" (in en). Comprehensive Glycoscience. pp. 373–396. doi:10.1016/B978-044451967-2/00040-4. ISBN 9780444519672. https://www.sciencedirect.com/science/article/pii/B9780444519672000404.
- ↑ 2.0 2.1 2.2 Pai, Manjunath P. (2018), "Macrolides, Azalides, and Ketolides" (in en), 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, https://link.springer.com/chapter/10.1007/978-3-319-72416-4_2, retrieved 2021-04-18
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 So, Wonhee; Nicolau, David P. (2016), "Pharmacodynamics of Macrolides, Azalides, and Ketolides" (in en), 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, https://link.springer.com/protocol/10.1007/978-1-4939-3323-5_14, retrieved 2021-04-18
- ↑ Mutak, Stjepan (February 2007). "Azalides from Azithromycin to New Azalide Derivatives" (in en). 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?" (in en). 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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