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Identification
Name Gatifloxacin
Accession Number DB01044 (APRD00996)
Type small molecule
Groups approved
Description

Gatifloxacin is an antibiotic of the fourth-generation fluoroquinolone family, that like other members of that family, inhibits the bacterial enzymes DNA gyrase and topoisomerase IV. Bristol-Myers Squibb introduced Gatifloxacin in 1999 under the proprietary name Tequin® for the treatment of respiratory tract infections, having licensed the medication from Kyorin Pharmaceutical Company of Japan. Allergan produces an eye-drop formulation called Zymar®. Gatifloxacin is available as tablets and in various aqueous solutions for intravenous therapy. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Tequin
Zymar
Brand mixtures Not Available
Categories
  • Anti-Infective Agents
  • Quinolones
  • Antibiotics
CAS number 112811-59-3
Weight Average: 375.3941
Monoisotopic: 375.159434412
Chemical Formula C19H22FN3O4
InChI Key InChIKey=XUBOMFCQGDBHNK-UHFFFAOYSA-N
InChI
InChI=1S/C19H22FN3O4/c1-10-8-22(6-5-21-10)16-14(20)7-12-15(18(16)27-2)23(11-3-4-11)9-13(17(12)24)19(25)26/h7,9-11,21H,3-6,8H2,1-2H3,(H,25,26)
Plain Text
IUPAC Name
1-cyclopropyl-6-fluoro-8-methoxy-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
COC1=C2N(C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1)C1CC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Fluoroquinolones and Quinolones
  • Aminoquinolines and Derivatives
  • Hydroxyquinolines
Substructures
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Pyridines and Derivatives
  • Piperazines
  • Fluoroquinolones and Quinolones
  • Cyclopropane and Derivatives
  • Ethers
  • Benzene and Derivatives
  • 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 bronchitis, sinusitis, community-acquired pneumonia, and skin infections (abscesses, wounds) caused by S. pneumoniae, H. influenzae, S. aureus, M. pneumoniae, C. pneumoniae, L. pneumophila, S. pyogenes
Pharmacodynamics Gatifloxacin is a synthetic broad-spectrum 8-methoxyfluoroquinolone antibacterial agent for oral or intravenous administration. 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. Gatifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Mechanism of action The bactericidal action of Gatifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
Absorption Well absorbed from the gastrointestinal tract after oral administration with absolute bioavailability of gatifloxacin is 96%
Volume of distribution Not Available
Protein binding 20%
Metabolism
Gatifloxacin undergoes limited biotransformation in humans with less than 1% of the dose excreted in the urine as ethylenediamine and methylethylenediamine metabolites

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Gatifloxacin
    		Ethylenediamine Details
    Gatifloxacin
      		Methylethylenediamine Details
      Route of elimination Not Available
      Half life 7-14 hours
      Clearance Not Available
      Toxicity Not Available
      Affected organisms
      • Enteric bacteria and other eubacteria
      Pathways Not Available
      Pharmacoeconomics
      Manufacturers
      • Allergan inc
      • Allergan
      Packagers
      Dosage forms
      Form Route Strength
      Solution Ophthalmic
      Prices
      Unit description Cost Unit
      Zymar 0.3% Solution 5ml Bottle 87.53 USD bottle
      Zymar 0.3% eye drops 16.75 USD ml
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents
      Country Patent Number Approved Expires (estimated)
      United States 6333045 2000-02-20 2020-02-20
      United States 4980470 1992-12-15 2009-12-15
      Canada 2307632 2007-05-22 2019-08-20
      Canada 1340316 1999-01-12 2016-01-12
      Properties
      State solid
      Experimental Properties
      Property Value Source
      melting point 182-185 °C Not Available
      water solubility 60 mg/mL (at pH 4) Not Available
      logP 2.6 Not Available
      Predicted Properties
      Property Value Source
      water solubility 6.31e-01 g/l ALOGPS
      logP -0.23 ALOGPS
      logP -0.58 ChemAxon
      logS -2.8 ALOGPS
      pKa (strongest acidic) 5.69 ChemAxon
      pKa (strongest basic) 8.73 ChemAxon
      physiological charge 0 ChemAxon
      hydrogen acceptor count 7 ChemAxon
      hydrogen donor count 2 ChemAxon
      polar surface area 82.11 ChemAxon
      rotatable bond count 4 ChemAxon
      refractivity 98.82 ChemAxon
      polarizability 38.29 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference
      1. Park-Wyllie LY, Juurlink DN, Kopp A, Shah BR, Stukel TA, Stumpo C, Dresser L, Low DE, Mamdani MM: Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med. 2006 Mar 30;354(13):1352-61. Epub 2006 Mar 1. Pubmed
      2. Gurwitz JH: Serious adverse drug effects—seeing the trees through the forest. N Engl J Med. 2006 Mar 30;354(13):1413-5. Epub 2006 Mar 1. Pubmed
      External Links
      Resource Link
      KEGG Compound C07661 Link_out
      PubChem Compound 5379 Link_out
      PubChem Substance 46506159 Link_out
      ChemSpider 5186 Link_out
      ChEBI 5280 Link_out
      ChEMBL 5280 Link_out
      Therapeutic Targets Database DAP001387 Link_out
      PharmGKB PA449738 Link_out
      Drug Product Database 2243181 Link_out
      RxList http://www.rxlist.com/cgi/generic3/gatifloxacin.htm Link_out
      Drugs.com http://www.drugs.com/cdi/gatifloxacin-drops.html Link_out
      PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zym1676.shtml Link_out
      Wikipedia http://en.wikipedia.org/wiki/Gatifloxacin Link_out
      ATC Codes
      • J01MA16
      • S01AE06
      AHFS Codes
      • 52:04.04
      PDB Entries Not Available
      FDA label show (134 KB)
      MSDS show (57.3 KB)
      Interactions
      Drug Interactions
      Drug Interaction
      Aluminium Formation of non-absorbable complexes
      Amiodarone Increased risk of cardiotoxicity and arrhythmias
      Bepridil Increased risk of cardiotoxicity and arrhythmias
      Bretylium Increased risk of cardiotoxicity and arrhythmias
      Chlorpromazine Increased risk of cardiotoxicity and arrhythmias
      Digoxin Gatifloxacin increases the effect of digoxin
      Dihydroquinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
      Disopyramide Increased risk of cardiotoxicity and arrhythmias
      Fluphenazine Increased risk of cardiotoxicity and arrhythmias
      Iron Formation of non-absorbable complexes
      Iron Dextran Formation of non-absorbable complexes
      Magnesium Formation of non-absorbable complexes
      Magnesium oxide Formation of non-absorbable complexes
      Magnesium salicylate Formation of non-absorbable complexes
      Mesoridazine Increased risk of cardiotoxicity and arrhythmias
      Methotrimeprazine Increased risk of cardiotoxicity and arrhythmias
      Perphenazine Increased risk of cardiotoxicity and arrhythmias
      Prochlorperazine Increased risk of cardiotoxicity and arrhythmias
      Promazine Increased risk of cardiotoxicity and arrhythmias
      Promethazine Increased risk of cardiotoxicity and arrhythmias
      Propiomazine Increased risk of cardiotoxicity and arrhythmias
      Quinidine Increased risk of cardiotoxicity and arrhythmias
      Quinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
      Quinupristin This combination presents an increased risk of toxicity
      Sotalol Increased risk of cardiotoxicity and arrhythmias
      Sucralfate Formation of non-absorbable complexes
      Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
      Thiethylperazine Increased risk of cardiotoxicity and arrhythmias
      Thioridazine Increased risk of cardiotoxicity and arrhythmias
      Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
      Toremifene Additive 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.
      Trifluoperazine Increased risk of cardiotoxicity and arrhythmias
      Triflupromazine Increased risk of cardiotoxicity and arrhythmias
      Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
      Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
      Zinc Formation of non-absorbable complexes
      Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
      Food Interactions
      • Absorption does not seem to be affected by milk or calcium carbonate, however, gatifloxacin bioavailability appears significantly reduced when combined with Ensure™ (Cmax is reduced by about 50% while total drug exposure (AUC) is reduced by about 25%).
      • Drink liberally.
      • Take without regard to meals.
      Targets

      1. 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: P72524 Link_out
      Gene: gyrA Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Harding I, Simpson I: Fluoroquinolones: is there a different mechanism of action and resistance against Streptococcus pneumoniae? J Chemother. 2000 Oct;12 Suppl 4:7-15. Pubmed
      2. Rafii F, Park M, Novak JS: Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones. Antimicrob Agents Chemother. 2005 Feb;49(2):488-92. Pubmed
      3. Kays MB, Zhanel GG, Reimann MA, Jacobi J, Denys GA, Smith DW, Wack MF: Selection of a gyrA mutation and treatment failure with gatifloxacin in a patient with Streptococcus pneumoniae with a preexisting parC mutation. Pharmacotherapy. 2007 Feb;27(2):221-6. Pubmed
      4. Kim OK, Ohemeng K, Barrett JF: Advances in DNA gyrase inhibitors. Expert Opin Investig Drugs. 2001 Feb;10(2):199-212. Pubmed
      5. Hosaka M: [Antibacterial property and clinical effect of gatifloxacin, a novel quinolone antibacterial agent] Nippon Yakurigaku Zasshi. 2003 Jun;121(6):447-56. Pubmed
      6. Mdluli K, Ma Z: Mycobacterium tuberculosis DNA gyrase as a target for drug discovery. Infect Disord Drug Targets. 2007 Jun;7(2):159-68. Pubmed

      2. DNA gyrase subunit B

      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: P0A4L9 Link_out
      Gene: gyrB Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Harding I, Simpson I: Fluoroquinolones: is there a different mechanism of action and resistance against Streptococcus pneumoniae? J Chemother. 2000 Oct;12 Suppl 4:7-15. Pubmed
      2. Rafii F, Park M, Novak JS: Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones. Antimicrob Agents Chemother. 2005 Feb;49(2):488-92. Pubmed
      3. Kays MB, Zhanel GG, Reimann MA, Jacobi J, Denys GA, Smith DW, Wack MF: Selection of a gyrA mutation and treatment failure with gatifloxacin in a patient with Streptococcus pneumoniae with a preexisting parC mutation. Pharmacotherapy. 2007 Feb;27(2):221-6. Pubmed
      4. Kim OK, Ohemeng K, Barrett JF: Advances in DNA gyrase inhibitors. Expert Opin Investig Drugs. 2001 Feb;10(2):199-212. Pubmed
      5. Hosaka M: [Antibacterial property and clinical effect of gatifloxacin, a novel quinolone antibacterial agent] Nippon Yakurigaku Zasshi. 2003 Jun;121(6):447-56. Pubmed
      6. Mdluli K, Ma Z: Mycobacterium tuberculosis DNA gyrase as a target for drug discovery. Infect Disord Drug Targets. 2007 Jun;7(2):159-68. Pubmed

      3. 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 (By similarity)

      Organism class: bacterial
      UniProt ID: P72525 Link_out
      Gene: parC Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Harding I, Simpson I: Fluoroquinolones: is there a different mechanism of action and resistance against Streptococcus pneumoniae? J Chemother. 2000 Oct;12 Suppl 4:7-15. Pubmed
      2. Rafii F, Park M, Novak JS: Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones. Antimicrob Agents Chemother. 2005 Feb;49(2):488-92. Pubmed
      3. Kays MB, Zhanel GG, Reimann MA, Jacobi J, Denys GA, Smith DW, Wack MF: Selection of a gyrA mutation and treatment failure with gatifloxacin in a patient with Streptococcus pneumoniae with a preexisting parC mutation. Pharmacotherapy. 2007 Feb;27(2):221-6. Pubmed
      4. Hosaka M: [Antibacterial property and clinical effect of gatifloxacin, a novel quinolone antibacterial agent] Nippon Yakurigaku Zasshi. 2003 Jun;121(6):447-56. Pubmed
      5. Mdluli K, Ma Z: Mycobacterium tuberculosis DNA gyrase as a target for drug discovery. Infect Disord Drug Targets. 2007 Jun;7(2):159-68. Pubmed

      4. DNA topoisomerase 4 subunit B

      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 (By similarity)

      Organism class: bacterial
      UniProt ID: Q59961 Link_out
      Gene: parE Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Harding I, Simpson I: Fluoroquinolones: is there a different mechanism of action and resistance against Streptococcus pneumoniae? J Chemother. 2000 Oct;12 Suppl 4:7-15. Pubmed
      2. Rafii F, Park M, Novak JS: Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones. Antimicrob Agents Chemother. 2005 Feb;49(2):488-92. Pubmed
      3. Kays MB, Zhanel GG, Reimann MA, Jacobi J, Denys GA, Smith DW, Wack MF: Selection of a gyrA mutation and treatment failure with gatifloxacin in a patient with Streptococcus pneumoniae with a preexisting parC mutation. Pharmacotherapy. 2007 Feb;27(2):221-6. Pubmed
      4. Hosaka M: [Antibacterial property and clinical effect of gatifloxacin, a novel quinolone antibacterial agent] Nippon Yakurigaku Zasshi. 2003 Jun;121(6):447-56. Pubmed
      5. Mdluli K, Ma Z: Mycobacterium tuberculosis DNA gyrase as a target for drug discovery. Infect Disord Drug Targets. 2007 Jun;7(2):159-68. Pubmed
      Carriers

      1. Serum albumin

      Actions: other/unknown

      Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

      UniProt ID: P02768 Link_out
      Gene: ALB Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Guo M, Zou JW, Yi PG, Shang ZC, Hu GX, Yu QS: Binding interaction of gatifloxacin with bovine serum albumin. Anal Sci. 2004 Mar;20(3):465-70. Pubmed
      2. Tan F, Guo M, Yu Q: Studies on interaction between gatifloxacin and human serum albumin as well as effect of copper(II) on the reaction. Spectrochim Acta A Mol Biomol Spectrosc. 2005 Oct;61(13-14):3006-12. Epub 2004 Dec 19. Pubmed
      Comments
      Drug created on June 13, 2005 07:24 / Updated on June 10, 2013 00:23