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Identification
Name Levofloxacin
Accession Number DB01137 (APRD00477)
Type small molecule
Groups approved
Description

A synthetic fluoroquinolone (fluoroquinolones) antibacterial agent that inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • L-Ofloxacin
  • levofloxacin
Brand names
  • Cravit
  • Cravit Ophthalmic
  • Elequine
  • Floxel
  • Iquix
  • Leroxacin
  • Lesacin
  • Levaquin
  • Levokacin
  • Levox
  • Levoxacin
  • Mosardal
  • Nofaxin
  • Quixin
  • Reskuin
  • Tavanic
  • Volequin
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Quinolones
  • Nucleic Acid Synthesis Inhibitors
  • Anti-Infective Agents, Urinary
CAS number 100986-85-4
Weight Average: 361.3675
Monoisotopic: 361.143784348
Chemical Formula C18H20FN3O4
InChI Key InChIKey=GSDSWSVVBLHKDQ-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
Plain Text
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-5,7,9(13),11-tetraene-11-carboxylic acid
SMILES
C[C@H]1COC2=C(N3CCN(C)CC3)C(F)=CC3=C2N1C=C(C(O)=O)C3=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Fluoroquinolones and Quinolones
  • Aminoquinolines and Derivatives
  • Hydroxyquinolines
Substructures
  • Hydroxy Compounds
  • Acetates
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Piperazines
  • Fluoroquinolones and Quinolones
  • Ethers
  • Benzene and Derivatives
  • Oxazines
  • Aminoquinolines and Derivatives
  • Carboxylic Acids and Derivatives
  • Hydroxyquinolines
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • (Iso)quinolines and Derivatives
  • Aryl Halides
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For 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.
Pharmacodynamics Levofloxacin, 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 action Levofloxacin 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.
Absorption Absorption 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 distribution Not Available
Protein binding 24-38% (to plasma proteins)
Metabolism

Mainly excreted as unchanged drug (87%); undergoes limited metabolism in humans.
Route of elimination Mainly excreted as unchanged drug in the urine.
Half life 6-8 hours
Clearance Not Available
Toxicity Side 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ortho mcneil pharmaceutical inc
  • Santen inc
  • Ortho mcneil janssen pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Solution Intravenous 125 mg/5 ml
Tablet, film coated Oral 250 mg
Tablet, film coated Oral 500 mg
Tablet, film coated Oral 750 mg
Prices
Unit description Cost Unit
Iquix 1.5% Solution 5ml Bottle 81.68 USD bottle
Levofloxacin hemihydr 100% powder 42.69 USD g
Levaquin 750 mg tablet 28.06 USD each
Levaquin 750 mg leva-pak tablet 27.51 USD tablet
Levaquin 500 mg tablet 16.57 USD tablet
Iquix 1.5% eye drops 15.71 USD ml
Levaquin 250 mg tablet 13.71 USD tablet
Quixin 0.5% eye drops 12.21 USD ml
Quixin 0.5% Solution 11.4 USD ml
Levaquin i.v. 25 mg/ml vial 1.94 USD ml
Levaquin 500 mg/100 ml d5w 0.44 USD ml
Patents
Country Patent Number Approved Expires
United States 6806256 2002-08-26 2022-08-26
United States 5053407 1993-12-20 2010-12-20
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Insoluble PhysProp
logP 2.1 PhysProp
Predicted Properties
Property Value Source
water solubility 1.44e+00 g/l ALOGPS
logP -0.02 ALOGPS
logP 0.65 ChemAxon Molconvert
logS -2.40 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 7 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 73.32 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 94.94 ChemAxon Molconvert
polarizability 36.69 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07660 Link_out
PubChem Compound 149096 Link_out
PubChem Substance 46505134 Link_out
ChemSpider 131410 Link_out
BindingDB 50167506 Link_out
Therapeutic Targets Database DAP000160 Link_out
PharmGKB PA450214 Link_out
Drug Product Database 2248263 Link_out
RxList http://www.rxlist.com/cgi/generic2/quixin.htm Link_out
Drugs.com http://www.drugs.com/cdi/levofloxacin-drops.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/flo1181.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Levofloxacin Link_out
ATC Codes
  • J01MA12
  • S01AX19
AHFS Codes
  • 08:12.18
PDB Entries Not Available
FDA label show (139.1 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
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

Pharmacological action: yes
Actions: inhibitor

Topoisomerase IV is essential for chromosome segregation. It has relaxation of supercoiled DNA activity. Performs the decatenation events required during the replication of a circular DNA molecule

Organism class: bacterial
UniProt ID: P43702 Link_out
Gene: parC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

DNA gyrase negatively supercoils closed circular double- stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings

Organism class: bacterial
UniProt ID: P43700 Link_out
Gene: gyrA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks

Organism class: human
UniProt ID: P11388 Link_out
Gene: TOP2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: 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: substrate, 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. 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

Actions: substrate
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Organic cation/carnitine transporter 1

Actions: inhibitor

Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET)

UniProt ID: Q9H015 Link_out
Gene: SLC22A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:46

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.