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Identification
NameLomefloxacin
Accession NumberDB00978  (APRD01076)
TypeSmall Molecule
GroupsApproved
Description

Lomefloxacin is a fluoroquinolone antibiotic, used to treat bacterial infections including bronchitis and urinary tract infections. It is also used to prevent urinary tract infections prior to surgery.

Structure
Thumb
Synonyms
(+-)-1-Ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid
1,4-Dihydro-6,8-difluoro-1-ethyl-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid
LFLX
Lomefloxacine
Lomefloxacino
Lomefloxacinum
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BareonNot Available
MaxaquinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Lomefloxacin hydrochloride
Thumb
  • InChI Key: KXEBLAPZMOQCKO-UHFFFAOYNA-N
  • Monoisotopic Mass: 387.116125638
  • Average Mass: 387.809
DBSALT000795
Categories
UNIIL6BR2WJD8V
CAS number98079-51-7
WeightAverage: 351.3479
Monoisotopic: 351.139447899
Chemical FormulaC17H19F2N3O3
InChI KeyInChIKey=ZEKZLJVOYLTDKK-UHFFFAOYSA-N
InChI
InChI=1S/C17H19F2N3O3/c1-3-21-8-11(17(24)25)16(23)10-6-12(18)15(13(19)14(10)21)22-5-4-20-9(2)7-22/h6,8-9,20H,3-5,7H2,1-2H3,(H,24,25)
IUPAC Name
1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(N3CCNC(C)C3)C(F)=C12
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
  • Dihydroquinolone
  • Aminoquinoline
  • Dihydroquinoline
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Dialkylarylamine
  • Fluorobenzene
  • Benzenoid
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Aryl halide
  • Aryl fluoride
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • 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 bacterial infections of the respiratory tract (chronic bronchitis) and urinary tract, and as a pre-operative prophylactic to prevent urinary tract infection caused by: S.pneumoniae, H.influenzae, S.aureus, P.aeruginosa, E. cloacae, P. mirabilis, C. civersus, S. asprphyticus, E.coli, and K.pneumoniae.
PharmacodynamicsLomefloxacin is a fluoroquinolone antibiotic used to treat chronic bronchitis, as well as complicated and uncomplicated urinary tract infections. It is also used as a prophylactic or preventative treatment to prevent urinary tract infections in patients undergoing transrectal or transurethral surgical procedures. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter.
Mechanism of actionLomefloxacin is a bactericidal fluoroquinolone agent with activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of lomefloxacin results from interference with the activity of the bacterial enzymes DNA gyrase and topoisomerase IV, which are needed for the transcription and replication of bacterial DNA. DNA gyrase appears to be the primary quinolone target for gram-negative bacteria. Topoisomerase IV appears to be the preferential target in gram-positive organisms. Interference with these two topoisomerases results in strand breakage of the bacterial chromosome, supercoiling, and resealing. As a result DNA replication and transcription is inhibited.
Related Articles
AbsorptionRapid and nearly complete with approximately 95% to 98% of a single oral dose being absorbed.
Volume of distributionNot Available
Protein binding10%
Metabolism

Minimally metabolized although 5 metabolites have been identified in human urine. 65% appears as the parent drug in urine and 9% as the glucuronide metabolite.

Route of eliminationThe urinary excretion of lomefloxacin was virtually complete within 72 hours after cessation of dosing, with approximately 65% of the dose being recovered as parent drug and 9% as its glucuronide metabolite.
Half life8 hours
Clearance
  • 271 mL/min/1.73 m2 [creatinine clearance of 110 mL/min/1.73 m2]
  • 31 mL/min/1.73 m2 [creatinine clearance of 0 mL/min/1.73 m2]
ToxicityAdverse reactions include peripheral neuropathy, nervousness, agitation, anxiety, and phototoxic events (rash, itching, burning) due to sunlight exposure.
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+0.9919
Blood Brain Barrier-0.9856
Caco-2 permeable-0.5416
P-glycoprotein substrateSubstrate0.8953
P-glycoprotein inhibitor INon-inhibitor0.8699
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.7933
CYP450 2C9 substrateNon-substrate0.8591
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7284
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.933
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8497
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6283
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.7701
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9971 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8282
hERG inhibition (predictor II)Non-inhibitor0.6392
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Pharmacia corp
Packagers
  • GD Searle LLC
  • Unimed Pharmaceuticals Inc.
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point239-240.5 °CPhysProp
water solubility27.2 mg/mLNot Available
logP-0.30TAKACS-NOVAK,K ET AL. (1992)
Predicted Properties
PropertyValueSource
Water Solubility0.106 mg/mLALOGPS
logP0ALOGPS
logP-0.39ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)5.64ChemAxon
pKa (Strongest Basic)8.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.88 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity90.11 m3·mol-1ChemAxon
Polarizability34.8 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

DrugSyn.org

US4528287
General ReferencesNot Available
External Links
ATC CodesJ01MA07S01AE04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (88 KB)
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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:
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. Didier ES, Bowers L, Stovall ME, Kuebler D, Mittleider D, Brindley PJ, Didier PJ: Antimicrosporidial activity of (fluoro)quinolones in vitro and in vivo. Folia Parasitol (Praha). 2005 May;52(1-2):173-81. [PubMed:16004377 ]
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. Takenouchi T, Ishii C, Sugawara M, Tokue Y, Ohya S: Incidence of various gyrA mutants in 451 Staphylococcus aureus strains isolated in Japan and their susceptibilities to 10 fluoroquinolones. Antimicrob Agents Chemother. 1995 Jul;39(7):1414-8. [PubMed:7492077 ]
  4. Drusano GL, Johnson DE, Rosen M, Standiford HC: Pharmacodynamics of a fluoroquinolone antimicrobial agent in a neutropenic rat model of Pseudomonas sepsis. Antimicrob Agents Chemother. 1993 Mar;37(3):483-90. [PubMed:8384815 ]
  5. Gushchin AE, Ladygina VG, Govorun VM: [Role of mutations in parC and gyrA in forming resistance of Mycoplasma hominis to fluoroquinolones]. Mol Gen Mikrobiol Virusol. 1999;(4):19-24. [PubMed:10621934 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Ubiquitin binding
Specific Function:
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:
TOP2A
Uniprot ID:
P11388
Molecular Weight:
174383.88 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Symporter activity
Specific Function:
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3.
Gene Name:
SLC22A5
Uniprot ID:
O76082
Molecular Weight:
62751.08 Da
References
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [PubMed:10525100 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
References
  1. Sasabe H, Tsuji A, Sugiyama Y: Carrier-mediated mechanism for the biliary excretion of the quinolone antibiotic grepafloxacin and its glucuronide in rats. J Pharmacol Exp Ther. 1998 Mar;284(3):1033-9. [PubMed:9495864 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23