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Identification
NameMoxifloxacin
Accession NumberDB00218  (APRD00281)
Typesmall molecule
Groupsapproved, investigational
Description

Moxifloxacin is a synthetic fluoroquinolone antibiotic agent. Bayer AG developed the drug (initially called BAY 12-8039) and it is marketed worldwide (as the hydrochloride) under the brand name Avelox (in some countries also Avalox) for oral treatment.

Structure
Thumb
Synonyms
SynonymLanguageCode
1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-((4as,7as)-octahydro-6H-pyrrolo(3,4-b)pyridin-6-yl)-4-oxo-3-quinolinecarboxylic acidNot AvailableNot Available
MoxifloxacinNot AvailableNot Available
Salts
Name/CAS Structure Properties
Moxifloxacin Hydrochloride
186826-86-8
Thumb
  • InChI Key: IDIIJJHBXUESQI-DFIJPDEKSA-N
  • Monoisotopic Mass: 437.151762215
  • Average Mass: 437.892
DBSALT000387
Brand names
NameCompany
AveloxNot Available
MOXEZANot Available
VigamoxNot Available
Brand mixturesNot Available
Categories
CAS number354812-41-2
WeightAverage: 401.4314
Monoisotopic: 401.175084476
Chemical FormulaC21H24FN3O4
InChI KeyFABPRXSRWADJSP-MEDUHNTESA-N
InChI
InChI=1S/C21H24FN3O4/c1-29-20-17-13(19(26)14(21(27)28)9-25(17)12-4-5-12)7-15(22)18(20)24-8-11-3-2-6-23-16(11)10-24/h7,9,11-12,16,23H,2-6,8,10H2,1H3,(H,27,28)/t11-,16+/m0/s1
IUPAC Name
7-[(4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
[H][C@]12CN(C[C@@]1([H])NCCC2)C1=C(F)C=C2C(=O)C(=CN(C3CC3)C2=C1OC)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassQuinoline Carboxylic Acids
Direct parentQuinoline Carboxylic Acids
Alternative parentsFluoroquinolones; Hydroquinolones; Hydroxyquinolines; Hydroquinolines; Pyridinecarboxylic Acids; Pyrrolopyridines; Anisoles; Alkyl Aryl Ethers; Fluorobenzenes; Piperidines; Aryl Fluorides; Pyrrolidines; Polyols; Cyclic Alcohols and Derivatives; Tertiary Amines; Dialkylamines; Carboxylic Acids; Enolates; Polyamines; Organofluorides
Substituentshydroxyquinoline; dihydroquinolone; dihydroquinoline; pyrrolopyridine; pyridine carboxylic acid or derivative; pyridine carboxylic acid; phenol ether; anisole; fluorobenzene; alkyl aryl ether; pyridine; aryl halide; piperidine; benzene; aryl fluoride; pyrrolidine; cyclic alcohol; polyol; tertiary amine; polyamine; ether; enolate; secondary aliphatic amine; secondary amine; carboxylic acid derivative; carboxylic acid; amine; organohalogen; organofluoride; organonitrogen compound
Classification descriptionThis compound belongs to the quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at at least one position.
Pharmacology
IndicationFor the treatment of sinus and lung infections such as sinusitis, pneumonia, and secondary infections in chronic bronchitis. Also for the treatment of bacterial conjunctivitis (pinkeye).
PharmacodynamicsMoxifloxacin is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms: Corynebacterium species, Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri, Streptococcus pneumoniae, and Streptococcus viridans group. Aerobic Gram-negative microorganisms: Acinetobacter lwoffii, Haemophilus influenzae, and Haemophilus parainfluenzae. Other microorganisms: Chlamydia trachomatis.
Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.
Mechanism of actionThe bactericidal action of moxifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.
AbsorptionWell absorbed from the gastrointestinal tract. Absolute oral bioavailability is approximately 90%. Food has little effect on absorption.
Volume of distribution
  • 1.7 to 2.7 L/kg
Protein binding50% bound to serum proteins, independent of drug concentration.
Metabolism

Approximately 52% or oral or intravenous dose is metabolized via glucuronide and sulphate conjugation. The cytochrome P450 system is not involved in metabolism. The sulphate conjugate accounts for 38% of the dose, and the glucuronide conjugate accounts for 14% of the dose.

Route of eliminationApproximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces).
Half life11.5-15.6 hours (single dose, oral)
Clearance
  • 12 +/- 2 L/hr
ToxicitySymptoms of overdose include CNS and gastrointestinal effects such as decreased activity, somnolence, tremor, convulsions, vomiting, and diarrhea. The minimal lethal intravenous dose in mice and rats is 100 mg/kg.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9794
Blood Brain Barrier - 0.9597
Caco-2 permeable - 0.6093
P-glycoprotein substrate Substrate 0.8607
P-glycoprotein inhibitor I Non-inhibitor 0.7564
P-glycoprotein inhibitor II Non-inhibitor 0.7181
Renal organic cation transporter Non-inhibitor 0.7318
CYP450 2C9 substrate Non-substrate 0.8018
CYP450 2D6 substrate Non-substrate 0.8247
CYP450 3A4 substrate Non-substrate 0.5756
CYP450 1A2 substrate Non-inhibitor 0.7417
CYP450 2C9 substrate Non-inhibitor 0.7735
CYP450 2D6 substrate Non-inhibitor 0.8359
CYP450 2C19 substrate Non-inhibitor 0.7401
CYP450 3A4 substrate Non-inhibitor 0.8811
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5536
Ames test AMES toxic 0.6227
Carcinogenicity Non-carcinogens 0.9038
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.3267 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8092
hERG inhibition (predictor II) Non-inhibitor 0.6461
Pharmacoeconomics
Manufacturers
  • Bayer healthcare pharmaceuticals inc
  • Alcon inc
  • Bayer Healthcare Pharmaceuticals
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous
SolutionOphthalmic
TabletOral
Prices
Unit descriptionCostUnit
Vigamox 0.5% Solution 3ml Bottle90.72USDbottle
Vigamox 0.5% eye drops27.22USDml
Avelox 400 mg tablet16.68USDtablet
Avelox abc pack 400 mg tablet16.35USDtablet
Avelox iv 400 mg/250 ml0.17USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States65480792000-07-252020-07-25
United States49905171994-12-082011-12-08
Canada23422112009-05-262019-09-29
Canada13401141998-11-032015-11-03
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point238-242 °CNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
water solubility1.68e-01 g/lALOGPS
logP0.01ALOGPS
logP-0.5ChemAxon
logS-3.4ALOGPS
pKa (strongest acidic)5.69ChemAxon
pKa (strongest basic)9.42ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count7ChemAxon
hydrogen donor count2ChemAxon
polar surface area82.11ChemAxon
rotatable bond count4ChemAxon
refractivity106.22ChemAxon
polarizability41.24ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Manne Reddy, Sajja Eswaraiah, Vetukuri Venkata Naga Raju, Rapolu Kumar, Ningam Srinivasreddy, Vedantham Ravindra, “Crystalline form III of anhydrous moxifloxacin hydrochloride and a process for preparation thereof.” U.S. Patent US20050137227, issued June 23, 2005.

US20050137227
General Reference
  1. Ginsburg AS, Hooper N, Parrish N, Dooley KE, Dorman SE, Booth J, Diener-West M, Merz WG, Bishai WR, Sterling TR: Fluoroquinolone resistance in patients with newly diagnosed tuberculosis. Clin Infect Dis. 2003 Dec 1;37(11):1448-52. Epub 2003 Nov 4. Pubmed
External Links
ResourceLink
KEGG CompoundC07663
PubChem Compound152946
PubChem Substance46508509
ChemSpider134802
BindingDB50146367
Therapeutic Targets DatabaseDAP000158
PharmGKBPA450555
Drug Product Database2246414
RxListhttp://www.rxlist.com/cgi/generic3/vigamox.htm
Drugs.comhttp://www.drugs.com/cdi/moxifloxacin-drops.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ave1540.shtml
WikipediaMoxifloxacin
ATC CodesS01AE07J01MA14
AHFS Codes
  • 08:12.18
  • 52:04.04
PDB EntriesNot Available
FDA labelshow(162 KB)
MSDSshow(193 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of acenocoumarol.
AluminiumFormation of non-absorbable complexes
AmiodaroneIncreased risk of cardiotoxicity and arrhythmias
AnisindioneThe quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of anisindione.
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
BepridilIncreased risk of cardiotoxicity and arrhythmias
BretyliumIncreased risk of cardiotoxicity and arrhythmias
CalciumFormation of non-absorbable complexes
DicoumarolThe quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of dicumarol.
Dihydroquinidine barbiturateIncreased risk of cardiotoxicity and arrhythmias
DisopyramideIncreased risk of cardiotoxicity and arrhythmias
ErythromycinIncreased risk of cardiotoxicity and arrhythmias
IronFormation of non-absorbable complexes
Iron DextranFormation of non-absorbable complexes
JosamycinIncreased risk of cardiotoxicity and arrhythmias
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MagnesiumFormation of non-absorbable complexes
Magnesium oxideFormation of non-absorbable complexes
QuinidineIncreased risk of cardiotoxicity and arrhythmias
Quinidine barbiturateIncreased risk of cardiotoxicity and arrhythmias
QuinupristinThis combination presents an increased risk of toxicity
SotalolIncreased risk of cardiotoxicity and arrhythmias
SucralfateFormation of non-absorbable complexes
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
TizanidineMoxifloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
WarfarinThe quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of warfarin.
ZincFormation of non-absorbable complexes
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
  • Take without regard to meals. Drink liberally. Absorption is not affected by lipid-rich meals or yogourt.

Targets

1. DNA topoisomerase 4 subunit A

Kind: protein

Organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase 4 subunit A P43702 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Schafer J, Hovde LB, Simonson D, Rotschafer JC: In vitro pharmacodynamics of moxifloxacin versus levofloxacin against 4 strains of Streptococcus pneumoniae: 1 wild type, 2 first-step parC mutants, and 1 pump mutant. Diagn Microbiol Infect Dis. 2007 Oct 1;. Pubmed
  4. Deryke CA, Du X, Nicolau DP: Evaluation of bacterial kill when modelling the bronchopulmonary pharmacokinetic profile of moxifloxacin and levofloxacin against parC-containing isolates of Streptococcus pneumoniae. J Antimicrob Chemother. 2006 Sep;58(3):601-9. Epub 2006 Jul 19. Pubmed
  5. Perez-Vazquez M, Roman F, Aracil B, Canton R, Campos J: Laboratory detection of Haemophilus influenzae with decreased susceptibility to nalidixic acid, ciprofloxacin, levofloxacin, and moxifloxacin due to GyrA and ParC mutations. J Clin Microbiol. 2004 Mar;42(3):1185-91. Pubmed

2. DNA gyrase subunit A

Kind: protein

Organism: Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
DNA gyrase subunit A P43700 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Schmitz FJ, Hofmann B, Hansen B, Scheuring S, Luckefahr M, Klootwijk M, Verhoef J, Fluit A, Heinz HP, Kohrer K, Jones ME: Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus. J Antimicrob Chemother. 1998 Apr;41(4):481-4. Pubmed
  4. Brisse S, Milatovic D, Fluit AC, Verhoef J, Martin N, Scheuring S, Kohrer K, Schmitz FJ: Comparative in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes clinical isolates with alterations in GyrA and ParC proteins. Antimicrob Agents Chemother. 1999 Aug;43(8):2051-5. Pubmed
  5. Dridi L, Tankovic J, Burghoffer B, Barbut F, Petit JC: gyrA and gyrB mutations are implicated in cross-resistance to Ciprofloxacin and moxifloxacin in Clostridium difficile. Antimicrob Agents Chemother. 2002 Nov;46(11):3418-21. Pubmed

3. DNA topoisomerase 2-alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
DNA topoisomerase 2-alpha P11388 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Reuveni D, Halperin D, Shalit I, Priel E, Fabian I: Moxifloxacin enhances etoposide-induced cytotoxic, apoptotic and anti-topoisomerase II effects in a human colon carcinoma cell line. Int J Oncol. 2010 Aug;37(2):463-71. Pubmed
  3. Wohlkonig A, Chan PF, Fosberry AP, Homes P, Huang J, Kranz M, Leydon VR, Miles TJ, Pearson ND, Perera RL, Shillings AJ, Gwynn MN, Bax BD: Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat Struct Mol Biol. 2010 Sep;17(9):1152-3. Epub 2010 Aug 29. Pubmed

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