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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
Synonyms
SynonymLanguageCode
1-Cyclopropyl-1,4-dihydro-6-fluoro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acidNot AvailableNot Available
1-Cyclopropyl-6-fluoro- 8-methoxy-7-(3-methylpiperazin-1-yl)- 4-oxo-quinoline-3-carboxylic acidNot AvailableNot Available
AM 1155Not AvailableNot Available
GatifloxacineNot AvailableNot Available
GatifloxacinoNot AvailableNot Available
GatifloxacinumNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
TequinNot Available
ZymarNot Available
ZYMAXIDNot Available
Brand mixturesNot Available
Categories
CAS number112811-59-3
WeightAverage: 375.3941
Monoisotopic: 375.159434412
Chemical FormulaC19H22FN3O4
InChI KeyXUBOMFCQGDBHNK-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
Not Available
EthylenediamineDetails
Gatifloxacin
Not Available
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 Solubility0.631ALOGPS
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 Area82.11 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity98.82 m3·mol-1ChemAxon
Polarizability38.29 Å3ChemAxon
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.

Targets

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

Carriers

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

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:23