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Identification
NameAzithromycin
Accession NumberDB00207  (APRD00397)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
(2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)13-((2,6-Dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyl)oxy)-2-ethyl-3,4,10-trihydroxy-3,5,6,8,10,12,14-heptamethyl-11-((3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl)oxy)-1-oxa-6-azacyclopentadecan-15-oneNot AvailableNot Available
AzenilNot AvailableNot Available
AzifastNot AvailableNot Available
AzigramNot AvailableNot Available
AzimakrolNot AvailableNot Available
AzithromycineFrenchINN
AzithromycinumLatinINN
AzitromicinaSpanishNot Available
AzitrominNot AvailableNot Available
HemomycinNot AvailableNot Available
ZithromaxNot AvailableNot Available
ZmaxNot AvailableNot Available
Salts
Name/CAS Structure Properties
Azithromycin dihydrate
Thumb Not applicable DBSALT000882
Brand names
NameCompany
AzaSiteNot Available
AzenilNot Available
AzibiotNot Available
AzinNot Available
AzithrocinNot Available
AzitromaxNot Available
AztrinNot Available
HemomycinNot Available
MisultinaNot Available
PenaloxNot Available
SumamedNot Available
VinzamNot Available
ZifinNot Available
ZithromaxNot Available
ZitrocinNot Available
ZitrotekNot Available
ZmaxNot Available
Brand mixturesNot Available
Categories
CAS number83905-01-5
WeightAverage: 748.9845
Monoisotopic: 748.508525778
Chemical FormulaC38H72N2O12
InChI KeyMQTOSJVFKKJCRP-BICOPXKESA-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
IUPAC Name
(2R,3S,4R,5R,8R,10R,11R,12S,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@H](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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassMacrolides and Analogues
SubclassNot Available
Direct parentMacrolides and Analogues
Alternative parentsDihexoses; O-glycosyl Compounds; Amino Sugars; Oxanes; Tertiary Alcohols; Tertiary Amines; 1,2-Diols; Carboxylic Acid Esters; Secondary Alcohols; Acetals; Polyamines
Substituentsdisaccharide; amino sugar; saccharide; oxane; tertiary alcohol; carboxylic acid ester; polyol; secondary alcohol; 1,2-diol; tertiary amine; carboxylic acid derivative; ether; acetal; polyamine; amine; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the macrolides and analogues. These are organic compounds containing a lactone ring of at least twelve members.
Pharmacology
IndicationFor 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
PharmacodynamicsAzithromycin, 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 actionAzithromycin binds to the 50S subunit of the 70S bacterial ribosomes, and therefore inhibits RNA-dependent protein synthesis in bacterial cells.
AbsorptionBioavailability 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 bindingSerum 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 eliminationBiliary excretion of azithromycin, predominantly as unchanged drug, is a major route of elimination.
Half life68 hours
Clearance
  • apparent plasma cl=630 mL/min [following single 500 mg oral and i.v. doses]
ToxicityPotentially serious side effects of angioedema and cholestatic jaundice were reported
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategorySMPDB ID
Azithromycin Action PathwayDrug actionSMP00247
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.5518
Blood Brain Barrier - 0.9739
Caco-2 permeable - 0.7578
P-glycoprotein substrate Substrate 0.8765
P-glycoprotein inhibitor I Inhibitor 0.8513
P-glycoprotein inhibitor II Non-inhibitor 0.8893
Renal organic cation transporter Non-inhibitor 0.8753
CYP450 2C9 substrate Non-substrate 0.8373
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.6403
CYP450 1A2 substrate Non-inhibitor 0.9295
CYP450 2C9 substrate Non-inhibitor 0.9021
CYP450 2D6 substrate Non-inhibitor 0.8904
CYP450 2C19 substrate Non-inhibitor 0.9023
CYP450 3A4 substrate Non-inhibitor 0.9533
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9751
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.9397
Biodegradation Not ready biodegradable 0.9673
Rat acute toxicity 2.5423 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9929
hERG inhibition (predictor II) Non-inhibitor 0.8555
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
FormRouteStrength
Powder, for solutionIntravenous
Powder, for solutionOral
Powder, for suspensionOral
TabletOral
Prices
Unit descriptionCostUnit
Zithromax 3 1 gm Packets Box118.26USDbox
Azithromycin 2.5 gm bulk vial75.6USDeach
Zmax adult-ped 2 g/60 ml susp70.39USDeach
Zithromax Tri-Pak 3 500 mg tablet Disp Pack69.67USDdisp
Zithromax Z-Pak 6 250 mg tablet Disp Pack68.62USDdisp
Zmax 2 g/60 ml susp sr67.04USDeach
Zmax pediatric 2 g/60 ml susp67.04USDeach
Zithromax 200 mg/5ml Suspension 30ml Bottle52.0USDbottle
Zithromax 100 mg/5ml Suspension 15ml Bottle51.6USDbottle
Zithromax 200 mg/5ml Suspension 15ml Bottle50.46USDbottle
Zithromax 200 mg/5ml Suspension 22.5ml Bottle50.46USDbottle
Azithromycin 3 500 mg tablet Disp Pack48.52USDdisp
Azithromycin 6 250 mg tablet Disp Pack48.52USDdisp
Azasite 1% eye drops42.85USDml
Zithromax i.v. 500 mg vial34.39USDvial
Azithromycin 200 mg/5ml Suspension 15ml Bottle34.25USDbottle
Zithromax 600 mg tablet27.22USDtablet
Zithromax 500 mg tablet22.68USDtablet
Zithromax tri-pak 500 mg tablet22.24USDtablet
Azithromycin 600 mg tablet19.04USDtablet
Azithromycin 500 mg tablet15.87USDtablet
Trimox 125 mg/5ml Suspension 100ml Bottle11.99USDbottle
Trimox 125 mg/5ml Suspension 150ml Bottle11.99USDbottle
Trimox 250 mg/5ml Suspension 80ml Bottle11.99USDbottle
Zithromax 250 mg z-pak tablet11.12USDtablet
Azithromycin i.v. 500 mg vial11.09USDeach
Azithromycin powder10.89USDg
Zithromax 250 mg tablet9.41USDtablet
Azithromycin 250 mg tablet6.33USDtablet
Apo-Azithromycin 250 mg Tablet3.11USDtablet
Co Azithromycin 250 mg Tablet3.11USDtablet
Mylan-Azithromycin 250 mg Tablet3.11USDtablet
Novo-Azithromycin 250 mg Tablet3.11USDtablet
Phl-Azithromycin 250 mg Tablet3.11USDtablet
Pms-Azithromycin 250 mg Tablet3.11USDtablet
Ratio-Azithromycin 250 mg Tablet3.11USDtablet
Sandoz Azithromycin 250 mg Tablet3.11USDtablet
Zithromax 40 mg/ml Suspension1.7USDml
Zithromax 20 mg/ml Suspension1.2USDml
Novo-Azithromycin 40 mg/ml Suspension0.95USDml
Pms-Azithromycin 40 mg/ml Suspension0.95USDml
Sandoz Azithromycin 40 mg/ml Suspension0.95USDml
Novo-Azithromycin 20 mg/ml Suspension0.67USDml
Pms-Azithromycin 20 mg/ml Suspension0.67USDml
Sandoz Azithromycin 20 mg/ml Suspension0.67USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States69844032004-02-142024-02-14
United States51925351993-03-092010-03-09
Canada24676112010-03-302024-05-18
Canada21480712000-10-172015-04-27
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point114 °CPhysProp
water solubilityslightNot Available
logP4.02MCFARLAND,JW ET AL. (1997)
pKa8.74 (at 25 °C)MCFARLAND,JW ET AL. (1997)
Predicted Properties
PropertyValueSource
water solubility5.14e-01 g/lALOGPS
logP3.03ALOGPS
logP2.44ChemAxon
logS-3.2ALOGPS
pKa (strongest acidic)12.43ChemAxon
pKa (strongest basic)9.57ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count13ChemAxon
hydrogen donor count5ChemAxon
polar surface area180.08ChemAxon
rotatable bond count7ChemAxon
refractivity194.11ChemAxon
polarizability83.11ChemAxon
number of rings3ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

William Heggie, Zita Maria De Mouro Vaz Azevedo Mendes, “Process for the preparation of azithromycin.” U.S. Patent US6013778, issued November, 1994.

US6013778
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
ResourceLink
KEGG CompoundC06838
BindingDB50197040
ChEBI2955
ChEMBLCHEMBL529
Therapeutic Targets DatabaseDNC001539
PharmGKBPA448519
HETZIT
Drug Product Database2255340
RxListhttp://www.rxlist.com/cgi/generic/zithromax.htm
Drugs.comhttp://www.drugs.com/cdi/azithromycin-drops.html
WikipediaAzithromycin
ATC CodesJ01FA10S01AA26
AHFS Codes
  • 08:12.12.92
PDB EntriesNot Available
FDA labelshow(76.3 KB)
MSDSshow(73.9 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolAzithromycin may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration.
AnisindioneAzithromycin may increase the anticoagulant effect of anisindione by increasing its serum concentration.
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
CyclosporineThe macrolide, azithromycin, may increase the effect of cyclosporine.
DicoumarolAzithromycin may increase the anticoagulant effect of dicumarol by increasing its serum concentration.
DisopyramideThe macrolide, azithromycin, may increase the effect of disopyramide.
LovastatinThe macrolide antibiotic, azithromycin, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if azithromycin is initiated, discontinued or dose changed.
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
VismodegibP-glycoprotein inhibitors may increase the chance of adverse drug reactions.
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
WarfarinAzithromycin may increase the anticoagulant effect of warfarin by increasing its serum concentration.
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol decanoateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
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

Kind: nucleotide

Organism: Enteric bacteria and other eubacteria

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details

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

Kind: protein

Organism: Escherichia coli O157:H7

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
50S ribosomal protein L4 P60725 Details

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

Kind: protein

Organism: Escherichia coli O157:H7

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
50S ribosomal protein L22 P61177 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

3. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Lexicomp

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08