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Identification
Name Azithromycin
Accession Number DB00207 (APRD00397)
Type small molecule
Groups approved
Description

Azithromycin is a semi-synthetic macrolide antibiotic of the azalide class. Like other macrolide antibiotics, azithromycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit of the bacterial 70S ribosome. Binding inhibits peptidyl transferase activity and interferes with amino acid translocation during the process of translation. Its effects may be bacteriostatic or bactericidal depending of the organism and the drug concentration. Its long half life, which enables once daily dosing and shorter administration durations, is a property distinct from other macrolides.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Aritromicina [Spanish]
  • Azithramycine
  • Azithromycin Dihydrate
  • Azithromycine [French]
  • Azithromycinum [Latin]
Brand names
  • Azenil
  • Azibiot
  • Azifine
  • Azitromax
  • Aziwok
  • Aztrin
  • Hemomycin
  • Misultina
  • Mixoterin
  • Setron
  • Sumamed
  • Tobil
  • Tromix
  • Vinzam
  • Zeto
  • Zifin
  • Zithrax
  • Zithromax
  • Zitrim
  • Zitrocin
  • Zitromax
  • Zitrotek
  • Zmax
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Other Macrolides
  • Macrolides
CAS number 83905-01-5
Weight Average: 748.9845
Monoisotopic: 748.508525778
Chemical Formula C38H72N2O12
InChI Key InChIKey=MQTOSJVFKKJCRP-OHJWJPDZSA-N
InChI
InChI=1S/C38H72N2O12/c1-15-27-38(10,46)31(42)24(6)40(13)19-20(2)17-36(8,45)33(52-35-29(41)26(39(11)12)16-21(3)48-35)22(4)30(23(5)34(44)50-27)51-28-18-37(9,47-14)32(43)25(7)49-28/h20-33,35,41-43,45-46H,15-19H2,1-14H3/t20-,21-,22?,23-,24-,25+,26+,27-,28+,29-,30+,31-,32+,33-,35+,36-,37-,38-/m1/s1
Plain Text
IUPAC Name
(2R,3S,4R,5R,8R,10R,11R,13S,14R)-11-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-2-ethyl-3,4,10-trihydroxy-13-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-3,5,6,8,10,12,14-heptamethyl-1-oxa-6-azacyclopentadecan-15-one
SMILES
CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)C(C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C)(O)C[C@@H](C)CN(C)[C@H](C)[C@@H](O)[C@]1(C)O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Macrolides
Substructures
  • Carboxylic Acids and Derivatives
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Acetates
  • Acetals and Derivatives
  • Lactones
  • Ethers
  • Aliphatic and Aryl Amines
  • Macrolides
  • Alcohols and Polyols
  • Heterocyclic compounds
Pharmacology
Indication For the treatment of patients with mild to moderate infections caused by susceptible strains of the designated microorganisms in the specific conditions: H. influenzae, M. catarrhalis, S. pneumoniae, C. pneumoniae, M. pneumoniae, S. pyogenes, S. aureus, S. agal
Pharmacodynamics Azithromycin, a semisynthetic antibiotic belonging to the macrolide subgroup of azalides, is used to treat STDs due to chlamydia and gonorrhea, community-acquired pneumonia, pelvic inflammatory disease, pediatric otitis media and pharyngitis, and Mycobacterium avium complex (MAC) in patients with advanced HIV disease. Similar in structure to erythromycin. azithromycin reaches higher intracellular concentrations than erythromycin, increasing its efficacy and duration of action.
Mechanism of action Azithromycin binds to the 50S subunit of the 70S bacterial ribosomes, and therefore inhibits RNA-dependent protein synthesis in bacterial cells.
Absorption Bioavailability is 37% following oral administration. Absorption is not affected by food. Azithromycin is extensively distributed in tissues with tissue concentrations reaching up to 50 times greater than plasma concentrations. Drug becomes concentrated within macrophages and polymorphonucleocytes giving it good activity against Chlamydia trachomatis.
Volume of distribution
  • 31.1 L/kg
Protein binding Serum protein binding is variable in the concentration range approximating human exposure, decreasing from 51% at 0.02 µg/mL to 7% at 2 µg/mL.
Metabolism

Hepatic. In vitro and in vivo studies to assess the metabolism of azithromycin have not been performed.
Route of elimination Biliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination.
Half life 68 hours
Clearance
  • apparent plasma cl=630 mL/min [following single 500 mg oral and i.v. doses]
Toxicity Potentially serious side effects of angioedema and cholestatic jaundice were reported
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Pathway Name SMPDB ID
Smp00247 Azithromycin Pathway SMP00247
Pharmacoeconomics
Manufacturers
  • Pfizer chemicals div pfizer inc
  • Pfizer global research development
  • Pliva inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Pfizer central research
  • App pharmaceuticals llc
  • Gland pharma ltd
  • Hospira inc
  • Pliva hrvatska doo
  • Sagent strides llc
  • Teva parenteral medicines inc
  • Pfizer inc
  • Inspire pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Wockhardt ltd
Packagers
Dosage forms
Form Route Strength
Powder, for solution Intravenous
Powder, for solution Oral
Powder, for suspension Oral
Tablet Oral
Prices
Unit description Cost Unit
Zithromax 3 1 gm Packets Box 118.26 USD box
Azithromycin 2.5 gm bulk vial 75.6 USD each
Zmax adult-ped 2 g/60 ml susp 70.39 USD each
Zithromax Tri-Pak 3 500 mg tablet Disp Pack 69.67 USD disp
Zithromax Z-Pak 6 250 mg tablet Disp Pack 68.62 USD disp
Zmax 2 g/60 ml susp sr 67.04 USD each
Zmax pediatric 2 g/60 ml susp 67.04 USD each
Zithromax 200 mg/5ml Suspension 30ml Bottle 52.0 USD bottle
Zithromax 100 mg/5ml Suspension 15ml Bottle 51.6 USD bottle
Zithromax 200 mg/5ml Suspension 15ml Bottle 50.46 USD bottle
Zithromax 200 mg/5ml Suspension 22.5ml Bottle 50.46 USD bottle
Azithromycin 3 500 mg tablet Disp Pack 48.52 USD disp
Azithromycin 6 250 mg tablet Disp Pack 48.52 USD disp
Azasite 1% eye drops 42.85 USD ml
Zithromax i.v. 500 mg vial 34.39 USD vial
Azithromycin 200 mg/5ml Suspension 15ml Bottle 34.25 USD bottle
Zithromax 600 mg tablet 27.22 USD tablet
Zithromax 500 mg tablet 22.68 USD tablet
Zithromax tri-pak 500 mg tablet 22.24 USD tablet
Azithromycin 600 mg tablet 19.04 USD tablet
Azithromycin 500 mg tablet 15.87 USD tablet
Trimox 125 mg/5ml Suspension 100ml Bottle 11.99 USD bottle
Trimox 125 mg/5ml Suspension 150ml Bottle 11.99 USD bottle
Trimox 250 mg/5ml Suspension 80ml Bottle 11.99 USD bottle
Zithromax 250 mg z-pak tablet 11.12 USD tablet
Azithromycin i.v. 500 mg vial 11.09 USD each
Azithromycin powder 10.89 USD g
Zithromax 250 mg tablet 9.41 USD tablet
Azithromycin 250 mg tablet 6.33 USD tablet
Apo-Azithromycin 250 mg Tablet 3.11 USD tablet
Co Azithromycin 250 mg Tablet 3.11 USD tablet
Mylan-Azithromycin 250 mg Tablet 3.11 USD tablet
Novo-Azithromycin 250 mg Tablet 3.11 USD tablet
Phl-Azithromycin 250 mg Tablet 3.11 USD tablet
Pms-Azithromycin 250 mg Tablet 3.11 USD tablet
Ratio-Azithromycin 250 mg Tablet 3.11 USD tablet
Sandoz Azithromycin 250 mg Tablet 3.11 USD tablet
Zithromax 40 mg/ml Suspension 1.7 USD ml
Zithromax 20 mg/ml Suspension 1.2 USD ml
Novo-Azithromycin 40 mg/ml Suspension 0.95 USD ml
Pms-Azithromycin 40 mg/ml Suspension 0.95 USD ml
Sandoz Azithromycin 40 mg/ml Suspension 0.95 USD ml
Novo-Azithromycin 20 mg/ml Suspension 0.67 USD ml
Pms-Azithromycin 20 mg/ml Suspension 0.67 USD ml
Sandoz Azithromycin 20 mg/ml Suspension 0.67 USD ml
Patents
Country Patent Number Approved Expires
United States 6984403 2004-02-14 2024-02-14
United States 5192535 1993-03-09 2010-03-09
Canada 2467611 2010-03-30 2024-05-18
Canada 2148071 2000-10-17 2015-04-27
Properties
State solid
Melting point 113-115 oC
Experimental Properties
Property Value Source
water solubility slight PhysProp
logP 4.02 [MCFARLAND,JW ET AL. (1997)] PhysProp
pKa 8.74 Various sources
Predicted Properties
Property Value Source
water solubility 5.14e-01 g/l ALOGPS
logP 3.03 ALOGPS
logP 2.44 ChemAxon Molconvert
logS -3.16 ALOGPS
pKa 12.90 ChemAxon Molconvert
hydrogen acceptor count 13 ChemAxon Molconvert
hydrogen donor count 5 ChemAxon Molconvert
polar surface area 180.08 ChemAxon Molconvert
rotatable bond count 7 ChemAxon Molconvert
refractivity 194.11 ChemAxon Molconvert
polarizability 82.40 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Noedl H, Krudsood S, Chalermratana K, Silachamroon U, Leowattana W, Tangpukdee N, Looareesuwan S, Miller RS, Fukuda M, Jongsakul K, Sriwichai S, Rowan J, Bhattacharyya H, Ohrt C, Knirsch C: Azithromycin combination therapy with artesunate or quinine for the treatment of uncomplicated Plasmodium falciparum malaria in adults: a randomized, phase 2 clinical trial in Thailand. Clin Infect Dis. 2006 Nov 15;43(10):1264-71. Epub 2006 Oct 12. Pubmed
External Links
Resource Link
KEGG Compound C06838 Link_out
PubChem Compound 55185 Link_out
PubChem Substance 46507743 Link_out
ChemSpider 49833 Link_out
BindingDB 50197040 Link_out
ChEBI 2955 Link_out
ChEMBL 2955 Link_out
Therapeutic Targets Database DNC001539 Link_out
PharmGKB PA448519 Link_out
HET ZIT Link_out
Drug Product Database 2255340 Link_out
RxList http://www.rxlist.com/cgi/generic/zithromax.htm Link_out
Drugs.com http://www.drugs.com/cdi/azithromycin-drops.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Azithromycin Link_out
ATC Codes
  • J01FA10
AHFS Codes
  • 08:12.12.92
PDB Entries Not Available
FDA label show (76.3 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Do not take Aluminum or magnesium antacids or supplements while on this medication.
  • Take on empty stomach: 1 hour before or 2 hours after meals.
Targets

1. 23S rRNA

Pharmacological action: yes
Actions: inhibitor

In prokaryotes, the 23S rRNA is part of the large subunit (the 50S) that joins with the 30S small subunit to create the functional 70S ribosome. The ribosome is comprised of 3 RNAs: the 23S, the 16S and the 5S ribosomal RNAs. The 23S and the 5S associate with their respective proteins to make up the large subunit of the ribosome, while the 16S RNA associates with its proteins to make up the small subunit.

Gene Sequence: FASTA

References:
  1. Ng LK, Martin I, Liu G, Bryden L: Mutation in 23S rRNA associated with macrolide resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2002 Sep;46(9):3020-5. Pubmed
  2. Jalava J, Vaara M, Huovinen P: Mutation at the position 2058 of the 23S rRNA as a cause of macrolide resistance in Streptococcus pyogenes. Ann Clin Microbiol Antimicrob. 2004 May 6;3:5. Pubmed
  3. Pereyre S, Renaudin H, Charron A, Bebear C, Bebear CM: Emergence of a 23S rRNA mutation in Mycoplasma hominis associated with a loss of the intrinsic resistance to erythromycin and azithromycin. J Antimicrob Chemother. 2006 Apr;57(4):753-6. Epub 2006 Feb 7. Pubmed

2. 50S ribosomal protein L4

Pharmacological action: yes
Actions: inhibitor

Forms part of the polypeptide exit tunnel (By similarity)

Organism class: bacterial
UniProt ID: P60725 Link_out
Gene: rplD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Halling SM, Jensen AE: Intrinsic and selected resistance to antibiotics binding the ribosome: analyses of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic implications. BMC Microbiol. 2006 Oct 2;6:84. Pubmed
  2. Tu D, Blaha G, Moore PB, Steitz TA: Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell. 2005 Apr 22;121(2):257-70. Pubmed
  3. Schlunzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A: Structural basis for the antibiotic activity of ketolides and azalides. Structure. 2003 Mar;11(3):329-38. Pubmed
  4. Petropoulos AD, Kouvela EC, Starosta AL, Wilson DN, Dinos GP, Kalpaxis DL: Time-resolved binding of azithromycin to Escherichia coli ribosomes. J Mol Biol. 2009 Jan 30;385(4):1179-92. Epub 2008 Nov 27. Pubmed
  5. Champney WS, Miller M: Inhibition of 50S ribosomal subunit assembly in Haemophilus influenzae cells by azithromycin and erythromycin. Curr Microbiol. 2002 Jun;44(6):418-24. Pubmed

3. 50S ribosomal protein L22

Pharmacological action: yes
Actions: inhibitor

The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome (By similarity)

Organism class: bacterial
UniProt ID: P61177 Link_out
Gene: rplV
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Halling SM, Jensen AE: Intrinsic and selected resistance to antibiotics binding the ribosome: analyses of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic implications. BMC Microbiol. 2006 Oct 2;6:84. Pubmed
  2. Tu D, Blaha G, Moore PB, Steitz TA: Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide a structural explanation for resistance. Cell. 2005 Apr 22;121(2):257-70. Pubmed
  3. Schlunzen F, Harms JM, Franceschi F, Hansen HA, Bartels H, Zarivach R, Yonath A: Structural basis for the antibiotic activity of ketolides and azalides. Structure. 2003 Mar;11(3):329-38. Pubmed
  4. Petropoulos AD, Kouvela EC, Starosta AL, Wilson DN, Dinos GP, Kalpaxis DL: Time-resolved binding of azithromycin to Escherichia coli ribosomes. J Mol Biol. 2009 Jan 30;385(4):1179-92. Epub 2008 Nov 27. Pubmed
  5. Champney WS, Miller M: Inhibition of 50S ribosomal subunit assembly in Haemophilus influenzae cells by azithromycin and erythromycin. Curr Microbiol. 2002 Jun;44(6):418-24. Pubmed
Enzymes

1. Cytochrome P450 2A6

Actions: inhibitor

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang E, Lew K, Barecki M, Casciano CN, Clement RP, Johnson WW: Quantitative distinctions of active site molecular recognition by P-glycoprotein and cytochrome P450 3A4. Chem Res Toxicol. 2001 Dec;14(12):1596-603. Pubmed
  2. Asakura E, Nakayama H, Sugie M, Zhao YL, Nadai M, Kitaichi K, Shimizu A, Miyoshi M, Takagi K, Takagi K, Hasegawa T: Azithromycin reverses anticancer drug resistance and modifies hepatobiliary excretion of doxorubicin in rats. Eur J Pharmacol. 2004 Jan 26;484(2-3):333-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.