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Identification
NameGatifloxacin
Accession NumberDB01044  (APRD00996)
Typesmall molecule
Groupsapproved, investigational
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
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
TequinNot Available
ZymarNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number112811-59-3
WeightAverage: 375.3941
Monoisotopic: 375.159434412
Chemical FormulaC19H22FN3O4
InChI KeyInChIKey=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)
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
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; Anisoles; Alkyl Aryl Ethers; Fluorobenzenes; Aryl Fluorides; Piperazines; Diazinanes; Tertiary Amines; Carboxylic Acids; Dialkylamines; Polyamines; Enolates; Organofluorides
Substituentsdihydroquinolone; hydroxyquinoline; dihydroquinoline; pyridine carboxylic acid or derivative; pyridine carboxylic acid; anisole; phenol ether; fluorobenzene; alkyl aryl ether; piperazine; benzene; aryl fluoride; aryl halide; pyridine; 1,4-diazinane; tertiary amine; polyamine; ether; secondary amine; secondary aliphatic amine; carboxylic acid derivative; carboxylic acid; enolate; organofluoride; amine; organonitrogen compound; organohalogen
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 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
PharmacodynamicsGatifloxacin 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 actionThe 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.
AbsorptionWell absorbed from the gastrointestinal tract after oral administration with absolute bioavailability of gatifloxacin is 96%
Volume of distributionNot Available
Protein binding20%
Metabolism

Gatifloxacin undergoes limited biotransformation in humans with less than 1% of the dose excreted in the urine as ethylenediamine and methylethylenediamine metabolites

SubstrateEnzymesProduct
Gatifloxacin
    EthylenediamineDetails
    Gatifloxacin
      MethylethylenediamineDetails
      Route of eliminationNot Available
      Half life7-14 hours
      ClearanceNot Available
      ToxicityNot Available
      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 + 0.9279
      Blood Brain Barrier - 0.9869
      Caco-2 permeable + 0.5
      P-glycoprotein substrate Substrate 0.9116
      P-glycoprotein inhibitor I Non-inhibitor 0.7838
      P-glycoprotein inhibitor II Non-inhibitor 0.6997
      Renal organic cation transporter Non-inhibitor 0.804
      CYP450 2C9 substrate Non-substrate 0.8257
      CYP450 2D6 substrate Non-substrate 0.9116
      CYP450 3A4 substrate Non-substrate 0.6231
      CYP450 1A2 substrate Non-inhibitor 0.8535
      CYP450 2C9 substrate Non-inhibitor 0.8479
      CYP450 2D6 substrate Non-inhibitor 0.9124
      CYP450 2C19 substrate Non-inhibitor 0.8598
      CYP450 3A4 substrate Non-inhibitor 0.8804
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7502
      Ames test AMES toxic 0.605
      Carcinogenicity Non-carcinogens 0.8678
      Biodegradation Not ready biodegradable 1.0
      Rat acute toxicity 2.3029 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.8994
      hERG inhibition (predictor II) Non-inhibitor 0.7207
      Pharmacoeconomics
      Manufacturers
      • Allergan inc
      • Allergan
      Packagers
      Dosage forms
      FormRouteStrength
      SolutionOphthalmic
      Prices
      Unit descriptionCostUnit
      Zymar 0.3% Solution 5ml Bottle87.53USDbottle
      Zymar 0.3% eye drops16.75USDml
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents
      CountryPatent NumberApprovedExpires (estimated)
      United States63330452000-02-202020-02-20
      United States49804701992-12-152009-12-15
      Canada23076322007-05-222019-08-20
      Canada13403161999-01-122016-01-12
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point182-185 °CNot Available
      water solubility60 mg/mL (at pH 4)Not Available
      logP2.6Not Available
      Predicted Properties
      PropertyValueSource
      water solubility6.31e-01 g/lALOGPS
      logP-0.23ALOGPS
      logP-0.58ChemAxon
      logS-2.8ALOGPS
      pKa (strongest acidic)5.69ChemAxon
      pKa (strongest basic)8.73ChemAxon
      physiological charge0ChemAxon
      hydrogen acceptor count7ChemAxon
      hydrogen donor count2ChemAxon
      polar surface area82.11ChemAxon
      rotatable bond count4ChemAxon
      refractivity98.82ChemAxon
      polarizability38.29ChemAxon
      number of rings4ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterNoChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      DrugSyn.org

      US4980470
      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
      ResourceLink
      KEGG CompoundC07661
      PubChem Compound5379
      PubChem Substance46506159
      ChemSpider5186
      ChEBI5280
      ChEMBLCHEMBL31
      Therapeutic Targets DatabaseDAP001387
      PharmGKBPA449738
      Drug Product Database2243181
      RxListhttp://www.rxlist.com/cgi/generic3/gatifloxacin.htm
      Drugs.comhttp://www.drugs.com/cdi/gatifloxacin-drops.html
      PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zym1676.shtml
      WikipediaGatifloxacin
      ATC CodesS01AE06J01MA16
      AHFS Codes
      • 52:04.04
      PDB EntriesNot Available
      FDA labelshow(134 KB)
      MSDSshow(57.3 KB)
      Interactions
      Drug Interactions
      Drug
      AluminiumFormation of non-absorbable complexes
      AmiodaroneIncreased risk of cardiotoxicity and arrhythmias
      BepridilIncreased risk of cardiotoxicity and arrhythmias
      BretyliumIncreased risk of cardiotoxicity and arrhythmias
      ChlorpromazineIncreased risk of cardiotoxicity and arrhythmias
      DigoxinGatifloxacin increases the effect of digoxin
      Dihydroquinidine barbiturateIncreased risk of cardiotoxicity and arrhythmias
      DisopyramideIncreased risk of cardiotoxicity and arrhythmias
      FluphenazineIncreased risk of cardiotoxicity and arrhythmias
      IronFormation of non-absorbable complexes
      Iron DextranFormation of non-absorbable complexes
      MagnesiumFormation of non-absorbable complexes
      Magnesium oxideFormation of non-absorbable complexes
      Magnesium salicylateFormation of non-absorbable complexes
      MesoridazineIncreased risk of cardiotoxicity and arrhythmias
      MethotrimeprazineIncreased risk of cardiotoxicity and arrhythmias
      PerphenazineIncreased risk of cardiotoxicity and arrhythmias
      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).
      ZincFormation of non-absorbable complexes
      ZiprasidoneAdditive 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.

      1. DNA gyrase subunit A

      Kind: protein

      Organism: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      DNA gyrase subunit A P72524 Details

      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

      Kind: protein

      Organism: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      DNA gyrase subunit B P0A4L9 Details

      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

      Kind: protein

      Organism: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      DNA topoisomerase 4 subunit A P72525 Details

      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

      Kind: protein

      Organism: Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      DNA topoisomerase 4 subunit B Q59961 Details

      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

      1. Serum albumin

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: other/unknown

      Components

      Name UniProt ID Details
      Serum albumin P02768 Details

      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 October 08, 2013 14:23