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Identification
NameLevofloxacin
Accession NumberDB01137  (APRD00477, DB06085)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A synthetic fluoroquinolone (fluoroquinolones) antibacterial agent that inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(-)-OfloxacinNot AvailableNot Available
(3S)-(-)-9-Fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acidNot AvailableNot Available
(S)-(-)-9-Fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzooxazine-6-carboxylic acidNot AvailableNot Available
(S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido(1,2,3-de)-1,4-benzoxazine-6-carboxylic acidNot AvailableNot Available
(S)-OfloxacinNot AvailableNot Available
L-ofloxacinNot AvailableNot Available
LevofloxacineNot AvailableNot Available
LevofloxacinoNot AvailableNot Available
LevofloxacinumNot AvailableNot Available
Ofloxacin S-(-)-formNot AvailableNot Available
Salts
Name/CAS Structure Properties
Levofloxacin hemihydrate
Thumb Not applicable DBSALT001001
Brand names
NameCompany
CravitNot Available
ElequineNot Available
FloxelNot Available
IquixNot Available
LeroxacinNot Available
LevaquinNot Available
LevokacinNot Available
LevoxNot Available
LevoxacinNot Available
MosardalNot Available
NofaxinNot Available
QuixinNot Available
ReskuinNot Available
TavanicNot Available
Brand mixturesNot Available
Categories
CAS number100986-85-4
WeightAverage: 361.3675
Monoisotopic: 361.143784348
Chemical FormulaC18H20FN3O4
InChI KeyGSDSWSVVBLHKDQ-JTQLQIEISA-N
InChI
InChI=1S/C18H20FN3O4/c1-10-9-26-17-14-11(16(23)12(18(24)25)8-22(10)14)7-13(19)15(17)21-5-3-20(2)4-6-21/h7-8,10H,3-6,9H2,1-2H3,(H,24,25)/t10-/m0/s1
IUPAC Name
(2S)-7-fluoro-2-methyl-6-(4-methylpiperazin-1-yl)-10-oxo-4-oxa-1-azatricyclo[7.3.1.0^{5,13}]trideca-5(13),6,8,11-tetraene-11-carboxylic acid
SMILES
C[C@H]1COC2=C3N1C=C(C(O)=O)C(=O)C3=CC(F)=C2N1CCN(C)CC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassQuinoline Carboxylic Acids
Direct parentQuinoline Carboxylic Acids
Alternative parentsFluoroquinolones; Hydroquinolones; Hydroxyquinolines; Benzoxazines; Hydroquinolines; Pyridinecarboxylic Acids; Alkyl Aryl Ethers; Fluorobenzenes; Piperazines; Diazinanes; Aryl Fluorides; Tertiary Amines; Carboxylic Acids; Enolates; Polyamines; Organofluorides
Substituentsdihydroquinolone; hydroxyquinoline; dihydroquinoline; benzoxazine; pyridine carboxylic acid or derivative; pyridine carboxylic acid; fluorobenzene; alkyl aryl ether; 1,4-diazinane; aryl halide; piperazine; benzene; aryl fluoride; pyridine; tertiary amine; polyamine; ether; enolate; carboxylic acid; carboxylic acid derivative; organonitrogen compound; amine; organohalogen; organofluoride
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 bacterial conjunctivitis caused by susceptible strains of the following organisms: Corynebacterium species, Staphylococus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus (Groups C/F/G), Viridans group streptococci, Acinetobacter lwoffii, Haemophilus influenzae, Serratia marcescens.
PharmacodynamicsLevofloxacin, a fluoroquinolone antiinfective, is the optically active L-isomer of ofloxacin. Levofloxacin is used to treat bacterial conjunctivitis, sinusitis, chronic bronchitis, community-acquired pneumonia and pneumonia caused by penicillin-resistant strains of Streptococcus pneumoniae, skin and skin structure infections, complicated urinary tract infections and acute pyelonephritis.
Mechanism of actionLevofloxacin inhibits bacterial type II topoisomerases, topoisomerase IV and DNA gyrase. Levofloxacin, like other fluoroquinolones, inhibits the A subunits of DNA gyrase, two subunits encoded by the gyrA gene. This results in strand breakage on a bacterial chromosome, supercoiling, and resealing; DNA replication and transcription is inhibited.
AbsorptionAbsorption of ofloxacin after single or multiple doses of 200 to 400 mg is predictable, and the amount of drug absorbed increases proportionately with the dose.
Volume of distributionNot Available
Protein binding24-38% (to plasma proteins)
Metabolism

Mainly excreted as unchanged drug (87%); undergoes limited metabolism in humans.

Route of eliminationMainly excreted as unchanged drug in the urine.
Half life6-8 hours
ClearanceNot Available
ToxicitySide effects include disorientation, dizziness, drowsiness, hot and cold flashes, nausea, slurring of speech, swelling and numbness in the face
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 Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
Manufacturers
  • Ortho mcneil pharmaceutical inc
  • Santen inc
  • Ortho mcneil janssen pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
SolutionIntravenous125 mg/5 ml
Tablet, film coatedOral250 mg
Tablet, film coatedOral500 mg
Tablet, film coatedOral750 mg
Prices
Unit descriptionCostUnit
Iquix 1.5% Solution 5ml Bottle81.68USDbottle
Levofloxacin hemihydr 100% powder42.69USDg
Levaquin 750 mg tablet28.06USDeach
Levaquin 750 mg leva-pak tablet27.51USDtablet
Levaquin 500 mg tablet16.57USDtablet
Iquix 1.5% eye drops15.71USDml
Levaquin 250 mg tablet13.71USDtablet
Quixin 0.5% eye drops12.21USDml
Quixin 0.5% Solution11.4USDml
Levaquin i.v. 25 mg/ml vial1.94USDml
Levaquin 500 mg/100 ml d5w0.44USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States68062562002-08-262022-08-26
United States50534071993-12-202010-12-20
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.44ALOGPS
logP-0.02ALOGPS
logP0.65ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)5.45ChemAxon
pKa (Strongest Basic)6.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area73.32 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity94.94 m3·mol-1ChemAxon
Polarizability36.69 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraMS/MS1D NMR2D NMR
References
Synthesis Reference

Valerie Niddam-Hildesheim, “Preparation of levofloxacin and forms thereof.” U.S. Patent US20030130507, issued July 10, 2003.

US20030130507
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07660
PubChem Compound149096
PubChem Substance46505134
ChemSpider131410
BindingDB50167506
Therapeutic Targets DatabaseDAP000160
PharmGKBPA450214
Drug Product Database2248263
RxListhttp://www.rxlist.com/cgi/generic2/quixin.htm
Drugs.comhttp://www.drugs.com/cdi/levofloxacin-drops.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/flo1181.shtml
WikipediaLevofloxacin
ATC CodesJ01MA12S01AE05
AHFS Codes
  • 08:12.18
PDB EntriesNot Available
FDA labelshow(139 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolThe quinolone antibiotic, levofloxacin, may increase the anticoagulant effect of acenocoumarol.
AluminiumFormation of non-absorbable complexes
AmiodaroneIncreased risk of cardiotoxicity and arrhythmias
AnisindioneThe quinolone antibiotic, levofloxacin, 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
Calcium AcetateCalcium salts such as calcium acetate may decrease the absorption of quinolone antibiotics such as levofloxacin. Of concern only with oral administration of both agents. Interactions can be minimized by administering oral quinolone at least 2 hours before, or 6 hours after, the dose of an oral calcium supplement. Monitor for decreased therapeutic effects of oral quinolones if administered with oral calcium supplements.
ChlorpromazineIncreased risk of cardiotoxicity and arrhythmias
DicoumarolThe quinolone antibiotic, levofloxacin, 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
FluphenazineIncreased 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
MesoridazineIncreased risk of cardiotoxicity and arrhythmias
MethotrimeprazineIncreased risk of cardiotoxicity and arrhythmias
PerphenazineIncreased risk of cardiotoxicity and arrhythmias
ProcainamideLevofloxacin may increase the effect of procainamide.
ProchlorperazineIncreased risk of cardiotoxicity and arrhythmias
PromazineIncreased risk of cardiotoxicity and arrhythmias
PromethazineIncreased risk of cardiotoxicity and arrhythmias
PropiomazineIncreased risk of cardiotoxicity and arrhythmias
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.
ThiethylperazineIncreased risk of cardiotoxicity and arrhythmias
ThioridazineIncreased risk of cardiotoxicity and arrhythmias
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to 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.
TrifluoperazineIncreased risk of cardiotoxicity and arrhythmias
TriflupromazineIncreased risk of cardiotoxicity and arrhythmias
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, levofloxacin, 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).
Food Interactions
  • Take without regard to meals. Take with water, drink lliberally. Taking this product with orange juice can result in reduced quinolone plasma levels.

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. Zheng X, Johnson C, Lu Y, Yanagihara R, Hollingshead S, Crain M, Benjamin W Jr, Waites KB: Clinical isolates of Streptococcus pneumoniae resistant to levofloxacin contain mutations in both gyrA and parC genes. Int J Antimicrob Agents. 2001 Oct;18(4):373-8. Pubmed
  4. 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
  5. 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

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. Messina C, Cafiso V, Campanile F, Santagati M, Stefani S: Rapid method for detection of gyrA and grlA mutations in unrelated strains of Staphylococci susceptible and resistant to levofloxacin. New Microbiol. 2001 Oct;24(4):347-53. Pubmed

3. DNA topoisomerase 2-alpha

Kind: protein

Organism: Human

Pharmacological action: yes

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

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Bellon A, Perez-Garcia G, Coverdale JH, Chacko RC: Seizures associated with levofloxacin: case presentation and literature review. Eur J Clin Pharmacol. 2009 Oct;65(10):959-62. Epub 2009 Aug 26. Pubmed
  2. 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: 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

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Ito T, Yano I, Tanaka K, Inui KI: Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J Pharmacol Exp Ther. 1997 Aug;282(2):955-60. Pubmed
  2. Yamaguchi H, Yano I, Hashimoto Y, Inui KI: Secretory mechanisms of grepafloxacin and levofloxacin in the human intestinal cell line caco-2. J Pharmacol Exp Ther. 2000 Oct;295(1):360-6. Pubmed
  3. Yamaguchi H, Yano I, Saito H, Inui K: Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats. Pharm Res. 2004 Feb;21(2):330-8. Pubmed

2. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Uwai Y, Okuda M, Takami K, Hashimoto Y, Inui K: Functional characterization of the rat multispecific organic anion transporter OAT1 mediating basolateral uptake of anionic drugs in the kidney. FEBS Lett. 1998 Nov 6;438(3):321-4. Pubmed

3. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

References:

  1. Urakami Y, Akazawa M, Saito H, Okuda M, Inui K: cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney. J Am Soc Nephrol. 2002 Jul;13(7):1703-10. Pubmed
  2. Okuda M, Urakami Y, Saito H, Inui K: Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim Biophys Acta. 1999 Mar 4;1417(2):224-31. Pubmed

4. Solute carrier family 22 member 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 4 Q9H015 Details

References:

  1. Yabuuchi H, Tamai I, Nezu J, Sakamoto K, Oku A, Shimane M, Sai Y, Tsuji A: Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999 May;289(2):768-73. Pubmed

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