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Identification
NameGemifloxacin
Accession NumberDB01155  (APRD00053)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Gemifloxacin is an oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. Gemifloxacin acts by inhibiting DNA synthesis through the inhibition of both DNA gyrase and topoisomerase IV, which are essential for bacterial growth.

Structure
Thumb
Synonyms
Factiv
Gemifloxacin mesilate
gemifloxacin mesylate
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Factivetablet320 mg/1oralMerus Labs International Inc.2003-04-04Not applicableUs
Factivetablet320 mgoralOscient Pharmaceuticals Corporation2006-11-242009-02-19Canada
Factivetablet320 mg/1oralVansen Pharma Inc.2003-04-04Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIOKR68Y0E4T
CAS number175463-14-6
WeightAverage: 389.3809
Monoisotopic: 389.149932358
Chemical FormulaC18H20FN5O4
InChI KeyInChIKey=ZRCVYEYHRGVLOC-HYARGMPZSA-N
InChI
InChI=1S/C18H20FN5O4/c1-28-22-14-8-23(6-9(14)5-20)17-13(19)4-11-15(25)12(18(26)27)7-24(10-2-3-10)16(11)21-17/h4,7,9-10H,2-3,5-6,8,20H2,1H3,(H,26,27)/b22-14+
IUPAC Name
7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
SMILES
CO\N=C1/CN(CC1CN)C1=NC2=C(C=C1F)C(=O)C(=CN2C1CC1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as naphthyridine carboxylic acids and derivatives. These are compounds containing a naphthyridine moiety, where one of the ring atoms bears a carboxylic acid group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassNaphthyridine carboxylic acids and derivatives
Direct ParentNaphthyridine carboxylic acids and derivatives
Alternative Parents
Substituents
  • Naphthyridine carboxylic acid
  • Fluoroquinolone
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Dialkylarylamine
  • Aminopyridine
  • Imidolactam
  • Pyridine
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Pyrrolidine
  • Tertiary amine
  • Oxime ether
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of bacterial infection caused by susceptible strains such as S. pneumoniae, H. influenzae, H. parainfluenzae, or M. catarrhalis, S. pneumoniae (including multi-drug resistant strains [MDRSP]), M. pneumoniae, C. pneumoniae, or K. pneumoniae.
PharmacodynamicsGemifloxacin is a quinolone/fluoroquinolone antibiotic. Gemifloxacin 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. Gemifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.
Mechanism of actionThe bactericidal action of gemifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination.
Related Articles
AbsorptionRapidly absorbed from the gastrointestinal tract. The absolute bioavailability averages approximately 71%.
Volume of distribution
  • 1.66 to 12.12 L/kg
Protein binding60-70%
Metabolism

Gemifloxacin is metabolized to a limited extent by the liver. All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin.

SubstrateEnzymesProduct
Gemifloxacin
Not Available
N-acetyl gemifloxacinDetails
Route of eliminationGemifloxacin and its metabolites are excreted via dual routes of excretion.Following oral administration of gemifloxacin to healthy subjects, a mean (± SD) of 61 ± 9.5% of the dose was excreted in the feces and 36 ± 9.3% in the urine as unchanged drug and metabolites. The mean (± SD) renal clearance following repeat doses of 320 mg was approximately 11.6 ± 3.9 L/hr (range 4.6-6 L/hr), which indicates active secretion is involved in the renal excretion of gemifloxacin.
Half life7 (± 2) hours
Clearance
  • renal cl=11.6+/- 3.9 L/hr [Healthy subjects receiving repeat doses of 320 mg orally]
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
PropertyValueProbability
Human Intestinal Absorption+0.9866
Blood Brain Barrier-0.5099
Caco-2 permeable-0.5644
P-glycoprotein substrateSubstrate0.8404
P-glycoprotein inhibitor INon-inhibitor0.85
P-glycoprotein inhibitor IIInhibitor0.6012
Renal organic cation transporterNon-inhibitor0.5751
CYP450 2C9 substrateNon-substrate0.8462
CYP450 2D6 substrateNon-substrate0.7919
CYP450 3A4 substrateNon-substrate0.5148
CYP450 1A2 substrateNon-inhibitor0.745
CYP450 2C9 inhibitorNon-inhibitor0.6642
CYP450 2D6 inhibitorNon-inhibitor0.809
CYP450 2C19 inhibitorNon-inhibitor0.6581
CYP450 3A4 inhibitorInhibitor0.5418
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7405
Ames testAMES toxic0.6124
CarcinogenicityNon-carcinogens0.7902
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5170 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8366
hERG inhibition (predictor II)Non-inhibitor0.6715
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral320 mg/1
Tabletoral320 mg
Prices
Unit descriptionCostUnit
Factive 5 320 mg tablet Box148.08USD box
Factive 320 mg tablet28.48USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5633262 No1995-06-152015-06-15Us
US5776944 No1997-04-042017-04-04Us
US6262071 No1999-09-212019-09-21Us
US6331550 No1999-09-212019-09-21Us
US6340689 No1999-09-142019-09-14Us
US6455540 No1999-09-212019-09-21Us
US6723734 No1998-03-202018-03-20Us
US6803376 No1999-09-212019-09-21Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityFreely soluble at neutral pH (350 mg/mL at 37 °C, pH 7.0).Not Available
logP2.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.21 mg/mLALOGPS
logP-0.82ALOGPS
logP-0.92ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)5.53ChemAxon
pKa (Strongest Basic)9.53ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area121.35 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity99.74 m3·mol-1ChemAxon
Polarizability39.3 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

US5633262
General ReferencesNot Available
External Links
ATC CodesJ01MA15
AHFS Codes
  • 08:12.18
PDB EntriesNot Available
FDA labelDownload (139 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Gemifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium carbonateCalcium carbonate can cause a decrease in the absorption of Gemifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
CitalopramGemifloxacin may increase the QTc-prolonging activities of Citalopram.
DicoumarolGemifloxacin may increase the anticoagulant activities of Dicoumarol.
DidanosineThe serum concentration of Didanosine can be decreased when it is combined with Gemifloxacin.
DofetilideGemifloxacin may increase the QTc-prolonging activities of Dofetilide.
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Gemifloxacin.
GoserelinGoserelin may increase the QTc-prolonging activities of Gemifloxacin.
InfliximabInfliximab may increase the neuroexcitatory activities of Gemifloxacin.
Insulin HumanGemifloxacin may increase the hypoglycemic activities of Insulin Regular.
Iron DextranThe serum concentration of Gemifloxacin can be decreased when it is combined with Iron Dextran.
IvabradineIvabradine may increase the QTc-prolonging activities of Gemifloxacin.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Gemifloxacin.
Magnesium oxideMagnesium oxide can cause a decrease in the absorption of Gemifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium SulfateThe serum concentration of Gemifloxacin can be decreased when it is combined with Magnesium Sulfate.
MifepristoneMifepristone may increase the QTc-prolonging activities of Gemifloxacin.
Mycophenolic acidThe serum concentration of Mycophenolic acid can be decreased when it is combined with Gemifloxacin.
OctreotideOctreotide may increase the QTc-prolonging activities of Gemifloxacin.
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Gemifloxacin.
PorfimerGemifloxacin may increase the photosensitizing activities of Porfimer.
ProbenecidProbenecid may decrease the excretion rate of Gemifloxacin which could result in a lower serum level and potentially a reduction in efficacy.
QuinaprilThe serum concentration of Gemifloxacin can be decreased when it is combined with Quinapril.
SevelamerSevelamer can cause a decrease in the absorption of Gemifloxacin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Strontium ranelateThe serum concentration of Gemifloxacin can be decreased when it is combined with Strontium ranelate.
SucralfateThe serum concentration of Gemifloxacin can be decreased when it is combined with Sucralfate.
VareniclineThe serum concentration of Varenicline can be increased when it is combined with Gemifloxacin.
VerteporfinGemifloxacin may increase the photosensitizing activities of Verteporfin.
Food Interactions
  • Take without regard to meals.

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
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.
Gene Name:
gyrA
Uniprot ID:
P43700
Molecular Weight:
97817.145 Da
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:17139284 ]
  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:17016423 ]
  3. Ruiz J, Marco F, Sierra JM, Aguilar L, Garcia-Mendez E, Mensa J, Jimenez De Anta MT, Vila J: In vitro activity of gemifloxacin against clinical isolates of Neisseria gonorrhoeae with and without mutations in the gyrA gene. Int J Antimicrob Agents. 2003 Jul;22(1):73-6. [PubMed:12842332 ]
  4. Alkorta M, Gimenez MJ, Vicente D, Aguilar L, Perez-Trallero E: In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point. Int J Antimicrob Agents. 2005 Feb;25(2):163-7. [PubMed:15664487 ]
  5. Yague G, Morris JE, Pan XS, Gould KA, Fisher LM: Cleavable-complex formation by wild-type and quinolone-resistant Streptococcus pneumoniae type II topoisomerases mediated by gemifloxacin and other fluoroquinolones. Antimicrob Agents Chemother. 2002 Feb;46(2):413-9. [PubMed:11796351 ]
Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
yes
Actions
inhibitor
General Function:
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function:
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.
Gene Name:
parC
Uniprot ID:
P43702
Molecular Weight:
83366.24 Da
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:17139284 ]
  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:17016423 ]
  3. Alkorta M, Gimenez MJ, Vicente D, Aguilar L, Perez-Trallero E: In vivo activity of gemifloxacin, moxifloxacin and levofloxacin against pneumococci with gyrA and parC point mutations in a sepsis mouse model measured with the all or nothing mortality end-point. Int J Antimicrob Agents. 2005 Feb;25(2):163-7. [PubMed:15664487 ]
  4. Yague G, Morris JE, Pan XS, Gould KA, Fisher LM: Cleavable-complex formation by wild-type and quinolone-resistant Streptococcus pneumoniae type II topoisomerases mediated by gemifloxacin and other fluoroquinolones. Antimicrob Agents Chemother. 2002 Feb;46(2):413-9. [PubMed:11796351 ]
  5. LaPlante KL, Rybak MJ, Tsuji B, Lodise TP, Kaatz GW: Fluoroquinolone resistance in Streptococcus pneumoniae: area under the concentration-time curve/MIC ratio and resistance development with gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin. Antimicrob Agents Chemother. 2007 Apr;51(4):1315-20. Epub 2007 Feb 12. [PubMed:17296740 ]
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Drug created on June 13, 2005 07:24 / Updated on July 29, 2016 01:52