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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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zymaxidsolution/ drops5 mg/mLophthalmicAllergan, Inc.2010-05-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zymaxidsolution/ drops5 mg/mLophthalmicPhysicians Total Care, Inc.2011-08-31Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Zymarsolution0.3 %ophthalmicAllergan IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gatifloxacinsolution/ drops5 mg/mLophthalmicHi Tech Pharmacal Co., Inc.2014-10-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Gatifloxacinsolution/ drops5 mg/mLophthalmicLupin Pharmaceuticals, Inc.2013-10-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
TequinNot Available
Brand mixturesNot Available
SaltsNot 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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassQuinoline carboxylic acids
Direct ParentQuinoline carboxylic acids
Alternative Parents
Substituents
  • Quinoline-3-carboxylic acid
  • N-arylpiperazine
  • Fluoroquinolone
  • Hydroxyquinoline
  • Dihydroquinolone
  • Aminoquinoline
  • Dihydroquinoline
  • Methoxyaniline
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Dialkylarylamine
  • Anisole
  • Fluorobenzene
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Ether
  • Secondary aliphatic amine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
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
  • Mycobacterium
  • Chlamydia pneumoniae
  • Chlamydia trachomatis
  • Mycoplasma pneumoniae
  • Legionella pneumophila
  • Chlamydia psittaci
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9279
Blood Brain Barrier-0.9869
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.9116
P-glycoprotein inhibitor INon-inhibitor0.7838
P-glycoprotein inhibitor IINon-inhibitor0.6997
Renal organic cation transporterNon-inhibitor0.804
CYP450 2C9 substrateNon-substrate0.8257
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6231
CYP450 1A2 substrateNon-inhibitor0.8535
CYP450 2C9 substrateNon-inhibitor0.8479
CYP450 2D6 substrateNon-inhibitor0.9124
CYP450 2C19 substrateNon-inhibitor0.8598
CYP450 3A4 substrateNon-inhibitor0.8804
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7502
Ames testAMES toxic0.605
CarcinogenicityNon-carcinogens0.8678
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3029 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8994
hERG inhibition (predictor II)Non-inhibitor0.7207
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Solutionophthalmic0.3 %
Solution/ dropsophthalmic5 mg/mL
Prices
Unit descriptionCostUnit
Zymar 0.3% Solution 5ml Bottle87.53USD bottle
Zymar 0.3% eye drops16.75USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
Canada13403161999-01-122016-01-12
Canada23076322007-05-222019-08-20
United States49804701992-12-152009-12-15
United States63330452000-02-202020-02-20
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 Solubility0.631 mg/mLALOGPS
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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesJ01MA16S01AE06
AHFS Codes
  • 52:04.04
PDB EntriesNot Available
FDA labelDownload (134 KB)
MSDSDownload (57.3 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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