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Identification
Name Ofloxacin
Accession Number DB01165 (APRD00502)
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 Not Available
Brand names
  • Akilen
  • Baccidal
  • Bactocin
  • Danoflox
  • Effexin
  • Exocin
  • Exocine
  • Flobacin
  • Flodemex
  • Flotavid
  • Flovid
  • Floxal
  • Floxil
  • Floxin
  • Floxstat
  • Fugacin
  • Inoflox
  • Kinflocin
  • Kinoxacin
  • Liflox
  • Loxinter
  • Marfloxacin
  • Medofloxine
  • Mergexin
  • Novecin
  • Nufafloqo
  • O-Flox
  • Obide
  • Occidal
  • Ofcin
  • Oflin
  • Oflocee
  • Oflocet
  • Oflocin
  • Oflodal
  • Oflodex
  • Oflodura
  • Oflox
  • Ofloxin
  • Ofus
  • Onexacin
  • Operan
  • Orocin
  • Otonil
  • Pharflox
  • Praxin
  • Puiritol
  • Qinolon
  • Qipro
  • Quinolon
  • Quotavil
  • Rilox
  • Sinflo
  • Tabrin
  • Taravid
  • Tariflox
  • Tarivid
  • Telbit
  • Tructum
  • Uro Tarivid
  • Viotisone
  • Zanocin
Brand name mixtures Not Available
Categories
  • Anti-Infectives
  • Anti-Bacterial Agents
  • Quinolones
  • Nucleic Acid Synthesis Inhibitors
  • Anti-Infective Agents, Urinary
CAS number 82419-36-1
Weight Average: 361.3675
Monoisotopic: 361.143784348
Chemical Formula C18H20FN3O4
InChI Key InChIKey=GSDSWSVVBLHKDQ-UHFFFAOYSA-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)
Plain Text
IUPAC Name
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
CC1COC2=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 infections (respiratory tract, kidney, skin, soft tissue, UTI), urethral and cervical gonorrhoea.
Pharmacodynamics Ofloxacin is a quinolone/fluoroquinolone antibiotic. Ofloxacin 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. Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.
Mechanism of action Ofloxacin acts on DNA gyrase and toposiomerase IV, enzymes which, like human topoisomerase, prevents the excessive supercoiling of DNA during replication or transcription. By inhibiting their function, the drug thereby inhibits normal cell division.
Absorption Bioavailability of ofloxacin in the tablet formulation is approximately 98%
Volume of distribution Not Available
Protein binding 32%
Metabolism

Hepatic
Route of elimination Elimination is mainly by renal excretion. Between 65% and 80% of an administered oral dose of ofloxacin is excreted unchanged via the kidneys within 48 hours of dosing. Four to eight percent of an ofloxacin dose is excreted in the feces. This indicates a small degree of biliary excretion of ofloxacin.
Half life 9 hours
Clearance Not Available
Toxicity LD50=5450 mg/kg (orally in mice)
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Ortho mcneil pharmaceutical inc
  • Bedford laboratories div ben venue laboratories inc
  • Akorn inc
  • Alcon inc
  • Bausch and lomb inc
  • Fdc ltd
  • Hi tech pharmacal co inc
  • Novex pharma
  • Pharmaforce inc
  • Sandoz inc
  • Daiichi pharmaceutical corp
  • Apotex inc
  • Bausch and lomb pharmaceuticals inc
  • Ortho mcneil janssen pharmaceuticals inc
  • Dr reddys laboratories ltd
  • Larken laboratories inc
  • Ranbaxy laboratories ltd
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Liquid Ophthalmic
Solution Ophthalmic
Tablet Oral
Prices
Unit description Cost Unit
Floxin Otic 0.3% Solution 10ml Bottle 142.91 USD bottle
Ofloxacin 10ml Otic (ear) Solution 132.19 USD bottle
Ofloxacin 10ml. Ophthalmic (eye) Solution 87.6 USD bottle
Floxin Otic 0.3% Solution 5ml Bottle 86.49 USD bottle
Ofloxacin 5ml Otic (ear) Solution 77.21 USD bottle
Ofloxacin 5ml. Ophthalmic (eye) Solution 43.86 USD bottle
Ocuflox 0.3% eye drops 11.35 USD ml
Floxin 400 mg tablet 9.55 USD tablet
Ofloxacin 0.3% eye drops 8.08 USD ml
Floxin 200 mg tablet 6.6 USD tablet
Ofloxacin 400 mg tablet 6.12 USD tablet
Ofloxacin 300 mg tablet 5.81 USD tablet
Floxin 300 mg tablet 5.61 USD tablet
Ofloxacin 200 mg tablet 4.88 USD tablet
Floxin otic singles 4.28 USD each
Ocuflox 0.3 % Solution 2.75 USD ml
Apo-Ofloxacin 0.3 % Solution 1.04 USD ml
Pms-Ofloxacin 0.3 % Solution 1.04 USD ml
Patents
Country Patent Number Approved Expires
United States 5401741 1995-03-27 2012-03-27
Properties
State solid
Melting point 250-257 oC
Experimental Properties
Property Value Source
water solubility 28.3 mg/mL 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 Drug D00453 Link_out
KEGG Compound C07321 Link_out
PubChem Compound 4583 Link_out
PubChem Substance 46507574 Link_out
ChemSpider 4422 Link_out
ChEBI 7731 Link_out
ChEMBL 7731 Link_out
Therapeutic Targets Database DAP000655 Link_out
PharmGKB PA450684 Link_out
HET XED Link_out
Drug Product Database 2243474 Link_out
RxList http://www.rxlist.com/cgi/generic/oflox.htm Link_out
Drugs.com http://www.drugs.com/cdi/ofloxacin-drops.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/flo1181.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Ofloxacin Link_out
ATC Codes
  • J01MA01
  • J01MA02
  • J01MA12
  • S01AX11
  • S01AX13
  • S01AX19
  • S03AA07
  • S02AA15
AHFS Codes
  • 08:12.18
  • 52:04.04
PDB Entries Not Available
FDA label show (197.7 KB)
MSDS show (73.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid high doses of caffeine.
  • Take without regard to meals.
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. Turner AK, Nair S, Wain J: The acquisition of full fluoroquinolone resistance in Salmonella Typhi by accumulation of point mutations in the topoisomerase targets. J Antimicrob Chemother. 2006 Oct;58(4):733-40. Epub 2006 Aug 8. Pubmed
  4. Chau TT, Campbell JI, Galindo CM, Van Minh Hoang N, Diep TS, Nga TT, Van Vinh Chau N, Tuan PQ, Page AL, Ochiai RL, Schultsz C, Wain J, Bhutta ZA, Parry CM, Bhattacharya SK, Dutta S, Agtini M, Dong B, Honghui Y, Anh DD, Canh DG, Naheed A, Albert MJ, Phetsouvanh R, Newton PN, Basnyat B, Arjyal A, La TT, Rang NN, Phuong LT, Van Be Bay P, von Seidlein L, Dougan G, Clemens JD, Vinh H, Hien TT, Chinh NT, Acosta CJ, Farrar J, Dolecek C: Salmonella enterica Serovar Typhi: Antimicrobial drug resistance in Asia and the molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother. 2007 Oct 1;. Pubmed
  5. Ishiguro F, Toho M, Yamazaki M, Matsuyuki S, Moriya K, Tanaka D, Isobe J, Kyota Y, Muraoka M: [Mutations of gyrA gene and parC gene in fluoroquinolone-resistant Escherichia coli isolates from sporadic diarrheal cases] Kansenshogaku Zasshi. 2006 Sep;80(5):507-12. Pubmed
  6. Drlica K, Zhao X: DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. 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. Cambau E, Sougakoff W, Besson M, Truffot-Pernot C, Grosset J, Jarlier V: Selection of a gyrA mutant of Mycobacterium tuberculosis resistant to fluoroquinolones during treatment with ofloxacin. J Infect Dis. 1994 Nov;170(5):1351. Pubmed
  5. Shi R, Zhang J, Li C, Kazumi Y, Sugawara I: Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing. J Clin Microbiol. 2006 Dec;44(12):4566-8. Epub 2006 Oct 11. Pubmed

3. DNA topoisomerase 2-alpha

Pharmacological action: unknown
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. Divo AA, Sartorelli AC, Patton CL, Bia FJ: Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro. Antimicrob Agents Chemother. 1988 Aug;32(8):1182-6. 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. 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. Organic cation/carnitine transporter 2

Actions: inhibitor

Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also Relative uptake activity ratio of carnitine to TEA is 11.3

UniProt ID: O76082 Link_out
Gene: SLC22A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

2. Multidrug resistance-associated protein 1

Actions: inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Terashi K, Oka M, Soda H, Fukuda M, Kawabata S, Nakatomi K, Shiozawa K, Nakamura T, Tsukamoto K, Noguchi Y, Suenaga M, Tei C, Kohno S: Interactions of ofloxacin and erythromycin with the multidrug resistance protein (MRP) in MRP-overexpressing human leukemia cells. Antimicrob Agents Chemother. 2000 Jun;44(6):1697-700. Pubmed

3. Solute carrier family 22 member 6

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

References:
  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed

4. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sasabe H, Tsuji A, Sugiyama Y: Carrier-mediated mechanism for the biliary excretion of the quinolone antibiotic grepafloxacin and its glucuronide in rats. J Pharmacol Exp Ther. 1998 Mar;284(3):1033-9. Pubmed

5. 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 April 19, 2011 15:08

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.