Azalides such as
azithromycin
Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of several bacterial infections. This includes otitis media, middle ear infections, strep throa ...
are a class of
macrolide
Macrolides are a class of mostly natural products with a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. Macrolides belong to the polyketide class of natural products. ...
antibiotics that were originally manufactured in response to the poor acid stability exhibited by original macrolides (
erythromycin
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...
). Following the clinical overuse of macrolides and azalides,
ketolides have been developed to combat surfacing macrolide-azalide resistance among streptococci species.
Azalides have several advantages over erythromycin such as more potent gram negative antimicrobial activity, acid stability, and side effect tolerability.
Although there are few drug interactions with azithromycin, it weakly inhibits the
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...
enzyme.
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.
Replacement of the ketone group in traditional macrolides with a tertiary amine group confers greater acid stability.
See
Beckmann rearrangement.
Mechanism of action
Azalides bind to the bacterial 50S ribosomal subunit and inhibit polypeptide elongation by hindering
peptidyl transfer RNA
Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...
translocation.
Pharmacokinetics
Applicable pharmacokinetic indexes are free azalide AUC
24/MIC because of the
post antibiotic effect they exhibit, and free azalide concentration/MIC.
[{{Cite journal, last=Jacobs, first=Michael R., date=March 2003, title=How can we predict bacterial eradication?, journal=International Journal of Infectious Diseases, language=en, volume=7, pages=S13–S20, doi=10.1016/s1201-9712(03)90066-x, pmid=12839703, issn=1201-9712, doi-access=free] Due to their large volume of distribution and lipophilic structure, azalides concentrate effectively in tissue.
References
Macrolide antibiotics