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Identification
Name Gemifloxacin
Accession Number DB01155 (APRD00053)
Type small molecule
Groups approved
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.
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Synonyms
  • Gemifloxacin mesilate
  • gemifloxacin mesylate
Synonyms
Gemifloxacin mesilate
gemifloxacin mesylate
Salts Not Available
Brand names
Name Company
Factive
Brand mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Quinolones
CAS number 175463-14-6
Weight Average: 389.3809
Monoisotopic: 389.149932358
Chemical Formula C18H20FN5O4
InChI Key InChIKey=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+
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For 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.
Pharmacodynamics Gemifloxacin 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 action The 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.
Absorption Rapidly absorbed from the gastrointestinal tract. The absolute bioavailability averages approximately 71%.
Volume of distribution
  • 1.66 to 12.12 L/kg
Protein binding 60-70%
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.
Route of elimination Gemifloxacin 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 life 7 (± 2) hours
Clearance
  • renal cl=11.6+/- 3.9 L/hr [Healthy subjects receiving repeat doses of 320 mg orally]
Toxicity Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Cornerstone therapeutics inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Factive 5 320 mg tablet Box 148.08 USD box
Factive 320 mg tablet 28.48 USD tablet
Patents
Country Patent Number Approved Expires (estimated)
United States 6262071 1999-09-21 2019-09-21
United States 5633262 1995-06-15 2015-06-15
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Freely soluble at neutral pH (350 mg/mL at 37oC, pH 7.0). PhysProp
logP 2.3 PhysProp
Predicted Properties
Property Value Source
water solubility 2.10e-01 g/l ALOGPS
logP -0.82 ALOGPS
logP -0.92 ChemAxon Molconvert
logS -3.3 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 9 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 121.35 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 99.74 ChemAxon Molconvert
polarizability 39.3 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02471 Link_out
ChEBI 101853 Link_out
ChEMBL 101853 Link_out
Therapeutic Targets Database DAP000851 Link_out
PharmGKB PA10088 Link_out
RxList http://www.rxlist.com/cgi/generic3/factive.htm Link_out
Drugs.com http://www.drugs.com/cdi/gemifloxacin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/fac1662.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Gemifloxacin Link_out
ATC Codes
  • J01MA15
AHFS Codes
  • 08:12.18
PDB Entries Not Available
FDA label show (139 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Aluminium Formation of non-absorbable complexes
Calcium Acetate Calcium salts such as calcium acetate may decrease the absorption of quinolone antibiotics such as gemifloxacin. Of concern only with oral administration of both agents. Interactions can be minimized by administering oral quinolone at least 2 hours before, or 6 hours after, the dose of an oral calcium supplement. Monitor for decreased therapeutic effects of oral quinolones if administered with oral calcium supplements.
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
Sucralfate Formation of non-absorbable complexes
Zinc Formation of non-absorbable complexes
Food Interactions
  • Take without regard to meals.
Targets

1. 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

Organism class: bacterial
UniProt ID: P43702 Link_out
Gene: parC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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

2. 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: P43700 Link_out
Gene: gyrA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2012 13:17