Editing Erythromycin (section)

== Pharmacology ==

=== Mechanism of action ===

Erythromycin displays [[bacteriostatic]] activity or inhibits growth of bacteria, especially at higher concentrations.<ref name = "Trevor_2010">{{cite book | chapter = Section VIII: Chemotherapeutic Drugs; Chapter 44: Chloramphenicol, Tetracyclines, Macrolides, Clindamycin, & Streptogramins | pages = 389–396 | veditors = Trevor AJ, Katzung BG, Masters SB |title = Katzung & Trevor's Pharmacology: Examination & Board Review |date=2010 |publisher=McGraw-Hill Medical |location=New York |isbn=978-0-07-170155-6 |edition=9th}}</ref> By binding to the 50s subunit of the bacterial [[rRNA]] complex, protein synthesis and subsequent structure and function processes critical for life or replication are inhibited.<ref name="Trevor_2010"/> Erythromycin interferes with aminoacyl translocation, preventing the transfer of the [[tRNA]] bound at the [[A site]] of the rRNA complex to the [[P site]] of the rRNA complex.<ref>{{cite web |url=https://www.sigmaaldrich.com/SE/en/product/sial/e6376 |title=Erythromycin |access-date=21 December 2023 |website=Sigma-Aldrich}}</ref> Without this translocation, the A site remains occupied, thus the addition of an incoming tRNA and its attached [[amino acid]] to the nascent [[polypeptide]] chain is inhibited.{{medical citation needed|date=December 2023}} This interferes with the production of functionally useful proteins, which is the basis of this antimicrobial action.{{medical citation needed|date=December 2023}}

Erythromycin increases gut motility by binding to [[motilin receptor]], thus it is a motilin receptor agonist in addition to its antimicrobial properties. It can be therefore administered intravenously as a stomach emptying stimulant.<ref>{{cite book |title=Gastroparesis: Pathophysiology, Clinical Presentation, Diagnosis and Treatment | vauthors = Parkman HP |publisher=Academic Press |year=2021 |pages=323–339 |chapter=Chapter 24 - Prokinetic agents for gastroparesis |doi=10.1016/B978-0-12-818586-5.00024-7 |isbn=9780128185865 |quote=Erythromycin has prokinetic effects because it is a motilin receptor agonist in addition to being an antibiotic. [...] When given intravenously, erythromycin is a potent stimulant of gastric emptying among the available prokinetic drugs. |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780128185865000247}}</ref>

=== Pharmacokinetics ===

Erythromycin is easily inactivated by gastric acid; therefore, all orally administered formulations are given as either enteric-coated or more-stable salts or [[ester]]s, such as erythromycin [[succinate|ethylsuccinate]]. Erythromycin is very rapidly absorbed, and diffuses into most tissues and [[phagocyte]]s. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where, during active [[phagocytosis]], large concentrations of erythromycin are released.<ref>{{cite journal | vauthors = Lebel M | title = Pharmacokinetic properties of clarithromycin: A comparison with erythromycin and azithromycin | journal = The Canadian Journal of Infectious Diseases | volume = 4 | issue = 3 | pages = 148–152 | date = May 1993 | pmid = 22346438 | pmc = 3250788 | doi = 10.1155/1993/168061 | doi-access = free }}</ref>

=== Metabolism ===

Most of erythromycin is metabolised by [[demethylation]] in the [[liver]] by the hepatic enzyme CYP3A4. Its main elimination route is in the [[bile]] with little renal excretion, 2%–15% unchanged drug. Erythromycin's [[elimination half-life]] ranges between 1.5 and 2.0 hours and is between 5 and 6 hours in patients with end-stage renal disease. Erythromycin levels peak in the serum 4 hours after dosing; ethylsuccinate peaks 0.5–2.5 hours after dosing, but can be delayed if digested with food.<ref name = "Edmunds_2009">{{cite book |vauthors=Edmunds MW, Mayhew MS |title=Pharmacology for the primary care provider |date=2009 |location=Saint Louis, Missouri | publisher = Elsevier Health Sciences |isbn=978-0-323-06316-6 |edition=Third |chapter=Chapter 61: Macrolides |pages=658–662 (661) |chapter-url=https://books.google.com/books?id=9JtgGU0fkggC&pg=PA661 |access-date=3 March 2022 |archive-date=23 May 2022 |archive-url=https://web.archive.org/web/20220523131602/https://books.google.com/books?id=9JtgGU0fkggC&pg=PA661 |url-status=live }}; {{cite book | vauthors = Kirst HA, Sides GD | date = 1993 | chapter = Chapter 28: Erythromycin | veditors = Bryskier A, Butzler JP, Neu HC, Tulkens | title = The Macrolides | publisher = Arnette-Blackwell | location = Oxford UK }}</ref>

Erythromycin crosses the placenta and enters breast milk. The American Association of Pediatrics determined erythromycin is safe to take while breastfeeding.<ref name="urlwww.breastfeedingmadesimple.com">{{cite journal | title = Transfer of drugs and other chemicals into human milk | journal = Pediatrics | volume = 108 | issue = 3 | pages = 776–89 | date = September 2001 | pmid = 11533352 | doi = 10.1542/peds.108.3.776 | author1 = American Academy of Pediatrics Committee on Drugs | doi-access = free }}</ref> Absorption in pregnant patients has been shown to be variable, frequently resulting in levels lower than in nonpregnant patients.<ref name="Philipson_1976">{{cite journal | vauthors = Philipson A, Sabath LD, Charles D | title = Erythromycin and clindamycin absorption and elimination in pregnant women | journal = Clinical Pharmacology and Therapeutics | volume = 19 | issue = 1 | pages = 68–77 | date = January 1976 | pmid = 1245094 | doi = 10.1002/cpt197619168 | s2cid = 7573420 }}</ref><ref name = "Briggs_2011" />