Identification

Name
Lomefloxacin
Accession Number
DB00978  (APRD01076)
Type
Small Molecule
Groups
Approved, Investigational
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
Product Ingredients
IngredientUNIICASInChI Key
Lomefloxacin hydrochloride9VC7S3ZXXB98079-52-8KXEBLAPZMOQCKO-UHFFFAOYSA-N
International/Other Brands
Bareon / Maxaquin
Categories
UNII
L6BR2WJD8V
CAS number
98079-51-7
Weight
Average: 351.3479
Monoisotopic: 351.139447899
Chemical Formula
C17H19F2N3O3
InChI Key
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

Pharmacology

Indication

For 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.

Structured Indications
Not Available
Pharmacodynamics

Lomefloxacin 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 action

Lomefloxacin 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.

TargetActionsOrganism
ADNA gyrase subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 4 subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
UDNA topoisomerase 2-alpha
inhibitor
Human
Absorption

Rapid and nearly complete with approximately 95% to 98% of a single oral dose being absorbed.

Volume of distribution
Not Available
Protein binding

10%

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 elimination

The 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 life

8 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]
Toxicity

Adverse reactions include peripheral neuropathy, nervousness, agitation, anxiety, and phototoxic events (rash, itching, burning) due to sunlight exposure.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Lomefloxacin can be increased when it is combined with Abiraterone.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Lomefloxacin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Lomefloxacin.Experimental
AzithromycinThe metabolism of Lomefloxacin can be decreased when combined with Azithromycin.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Lomefloxacin.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Lomefloxacin.Approved, Investigational
BortezomibThe metabolism of Lomefloxacin can be decreased when combined with Bortezomib.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Lomefloxacin.Approved
CaffeineThe metabolism of Lomefloxacin can be decreased when combined with Caffeine.Approved
CitalopramThe metabolism of Lomefloxacin can be decreased when combined with Citalopram.Approved
ClotrimazoleThe metabolism of Lomefloxacin can be decreased when combined with Clotrimazole.Approved, Vet Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Lomefloxacin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Lomefloxacin.Experimental
Cyproterone acetateThe serum concentration of Lomefloxacin can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DeferasiroxThe serum concentration of Lomefloxacin can be increased when it is combined with Deferasirox.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Lomefloxacin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Lomefloxacin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Lomefloxacin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Lomefloxacin.Approved, Investigational
DosulepinThe metabolism of Lomefloxacin can be decreased when combined with Dosulepin.Approved
FluvoxamineThe metabolism of Lomefloxacin can be decreased when combined with Fluvoxamine.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Lomefloxacin.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Lomefloxacin.Experimental
LidocaineThe metabolism of Lomefloxacin can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Lomefloxacin can be decreased when combined with Lobeglitazone.Approved, Investigational
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Lomefloxacin.Experimental
MexiletineThe metabolism of Lomefloxacin can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Lomefloxacin can be decreased when combined with Midostaurin.Approved
NevirapineThe metabolism of Lomefloxacin can be decreased when combined with Nevirapine.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Lomefloxacin.Experimental, Investigational
OsimertinibThe serum concentration of Lomefloxacin can be decreased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Lomefloxacin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Lomefloxacin.Approved, Vet Approved
Peginterferon alfa-2bThe serum concentration of Lomefloxacin can be increased when it is combined with Peginterferon alfa-2b.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Lomefloxacin.Experimental
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Lomefloxacin.Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Lomefloxacin.Experimental
RopiniroleThe metabolism of Lomefloxacin can be decreased when combined with Ropinirole.Approved, Investigational
SimeprevirThe metabolism of Lomefloxacin can be decreased when combined with Simeprevir.Approved
Tenofovir disoproxilThe metabolism of Lomefloxacin can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Lomefloxacin can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Lomefloxacin can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Lomefloxacin can be decreased when combined with Ticlopidine.Approved
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Lomefloxacin.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Lomefloxacin.Approved, Investigational
VemurafenibThe serum concentration of Lomefloxacin can be increased when it is combined with Vemurafenib.Approved
ZucapsaicinThe metabolism of Lomefloxacin can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

Synthesis Reference
US4528287
General References
Not Available
External Links
Human Metabolome Database
HMDB15113
KEGG Drug
D02318
KEGG Compound
C07078
PubChem Compound
3948
PubChem Substance
46508499
ChemSpider
3811
BindingDB
50417952
ChEBI
116278
ChEMBL
CHEMBL561
Therapeutic Targets Database
DAP000653
PharmGKB
PA164749165
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Lomefloxacin
ATC Codes
J01MA07 — LomefloxacinS01AE04 — Lomefloxacin
FDA label
Download (88 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Pharmacia corp
Packagers
  • GD Searle LLC
  • Unimed Pharmaceuticals Inc.
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)239-240.5 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Quinoline carboxylic acids
Direct Parent
Quinoline carboxylic acids
Alternative Parents
Fluoroquinolones / N-arylpiperazines / Haloquinolines / Hydroquinolones / Aminoquinolines and derivatives / Hydroquinolines / Pyridinecarboxylic acids / Dialkylarylamines / Benzenoids / Aryl fluorides
show 12 more
Substituents
Quinoline-3-carboxylic acid / Fluoroquinolone / N-arylpiperazine / Aminoquinoline / Haloquinoline / Dihydroquinolone / Dihydroquinoline / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Tertiary aliphatic/aromatic amine
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, quinolone antibiotic, fluoroquinolone antibiotic, quinolone, quinolinemonocarboxylic acid (CHEBI:116278)

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, inc...
Gene Name
gyrA
Uniprot ID
P43700
Uniprot Name
DNA gyrase subunit A
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
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
Uniprot Name
DNA topoisomerase 4 subunit A
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
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 segr...
Gene Name
TOP2A
Uniprot ID
P11388
Uniprot Name
DNA topoisomerase 2-alpha
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
Substrate
Inhibitor
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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 cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
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
Uniprot Name
Canalicular multispecific organic anion transporter 1
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]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:45