Identification

Name
Pefloxacin
Accession Number
DB00487  (APRD00108)
Type
Small Molecule
Groups
Approved
Description

A synthetic broad-spectrum fluoroquinolone antibacterial agent active against most gram-negative and gram-positive bacteria. [PubChem]

Structure
Thumb
Synonyms
  • Labocton
  • Pefloxacin
  • Pefloxacine
  • Pefloxacino
  • Pefloxacinum
  • PFLX
Product Ingredients
IngredientUNIICASInChI Key
Pefloxacin mesylate5IAD0UV3FH70458-95-6HQQSBEDKMRHYME-UHFFFAOYSA-N
Pefloxacin mesylate dihydrateCX28QC6FU0149676-40-4LEULAXMUNMRLPW-UHFFFAOYSA-N
International/Other Brands
Labocton
Categories
UNII
2H52Z9F2Q5
CAS number
70458-92-3
Weight
Average: 333.3574
Monoisotopic: 333.148869726
Chemical Formula
C17H20FN3O3
InChI Key
FHFYDNQZQSQIAI-UHFFFAOYSA-N
InChI
InChI=1S/C17H20FN3O3/c1-3-20-10-12(17(23)24)16(22)11-8-13(18)15(9-14(11)20)21-6-4-19(2)5-7-21/h8-10H,3-7H2,1-2H3,(H,23,24)
IUPAC Name
1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=CC(F)=C(C=C12)N1CCN(C)CC1

Pharmacology

Indication

For the treatment of uncomplicated gonococcal urethritis in males and for gram-negative-bacterial infections in the gastrointestinal system and the genitourinary tract.

Pharmacodynamics

Pefloxacin is a fluoroquinolone antibiotic. Flouroquinolones such as pefloxacin 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

The bactericidal action of pefloxacin 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 topoisomerase 4 subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA gyrase subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
UDNA topoisomerase 2-alpha
inhibitor
Human
UDNA topoisomerase 1
inhibitor
Staphylococcus aureus
Absorption

Well absorbed by the oral route.

Volume of distribution
Not Available
Protein binding

20-30%

Metabolism

Hepatic. Primary metabolites are pefloxacin N-oxide and norfloxacin.

Route of elimination
Not Available
Half life

8.6 hours

Clearance
Not Available
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
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Pefloxacin.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Pefloxacin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Pefloxacin.
3-isobutyl-1-methyl-7H-xanthineThe metabolism of 3-isobutyl-1-methyl-7H-xanthine can be decreased when combined with Pefloxacin.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Pefloxacin.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Pefloxacin.
7-DeazaguanineThe metabolism of 7-Deazaguanine can be decreased when combined with Pefloxacin.
7,9-DimethylguanineThe metabolism of 7,9-Dimethylguanine can be decreased when combined with Pefloxacin.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Pefloxacin.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Pefloxacin.
Food Interactions
Not Available

References

Synthesis Reference
US4292317
General References
Not Available
External Links
Human Metabolome Database
HMDB0014630
KEGG Drug
D02306
PubChem Compound
51081
PubChem Substance
46507338
ChemSpider
46291
BindingDB
57936
ChEBI
50199
ChEMBL
CHEMBL267648
Therapeutic Targets Database
DAP001001
PharmGKB
PA164742856
Wikipedia
Pefloxacin
ATC Codes
J01MA03 — Pefloxacin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)271 dec °CPhysProp
water solubility11.4 mg/mL at 25 °CNot Available
logP0.27HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility1.23 mg/mLALOGPS
logP0.2ALOGPS
logP0.88ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)5.66ChemAxon
pKa (Strongest Basic)6.47ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area64.09 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity90.77 m3·mol-1ChemAxon
Polarizability34.42 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9914
Blood Brain Barrier-0.9651
Caco-2 permeable+0.9002
P-glycoprotein substrateSubstrate0.8136
P-glycoprotein inhibitor INon-inhibitor0.8781
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.6812
CYP450 2C9 substrateNon-substrate0.8645
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6809
CYP450 1A2 substrateNon-inhibitor0.9275
CYP450 2C9 inhibitorNon-inhibitor0.9206
CYP450 2D6 inhibitorNon-inhibitor0.9112
CYP450 2C19 inhibitorNon-inhibitor0.8584
CYP450 3A4 inhibitorNon-inhibitor0.9524
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6784
Ames testAMES toxic0.9108
CarcinogenicityNon-carcinogens0.8816
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9255 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7983
hERG inhibition (predictor II)Non-inhibitor0.7795
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0198000000-230c93f5eaf4301ff8c6
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0910000000-593baa616326abe5f576

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
N-arylpiperazines / Fluoroquinolones / Aminoquinolines and derivatives / Hydroquinolones / Haloquinolines / Hydroquinolines / Pyridinecarboxylic acids / Dialkylarylamines / N-methylpiperazines / Aryl fluorides
show 13 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 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, N-alkylpiperazine, quinolone antibiotic, fluoroquinolone antibiotic, quinolone (CHEBI:50199)

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
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. Varon E, Houssaye S, Grondin S, Gutmann L: Nonmolecular test for detection of low-level resistance to fluoroquinolones in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2006 Feb;50(2):572-9. [PubMed:16436712]
  4. 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:15673722]
  5. Vila J, Sanchez-Cespedes J, Sierra JM, Piqueras M, Nicolas E, Freixas J, Giralt E: Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria. Int J Antimicrob Agents. 2006 Jul;28(1):19-24. Epub 2006 Jun 14. [PubMed:16781123]
  6. Oyamada Y, Ito H, Fujimoto K, Asada R, Niga T, Okamoto R, Inoue M, Yamagishi J: Combination of known and unknown mechanisms confers high-level resistance to fluoroquinolones in Enterococcus faecium. J Med Microbiol. 2006 Jun;55(Pt 6):729-36. [PubMed:16687591]
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. Gootz TD, Zaniewski RP, Haskell SL, Kaczmarek FS, Maurice AE: Activities of trovafloxacin compared with those of other fluoroquinolones against purified topoisomerases and gyrA and grlA mutants of Staphylococcus aureus. Antimicrob Agents Chemother. 1999 Aug;43(8):1845-55. [PubMed:10428901]
  4. Bebear CM, Renaudin H, Charron A, Bove JM, Bebear C, Renaudin J: Alterations in topoisomerase IV and DNA gyrase in quinolone-resistant mutants of Mycoplasma hominis obtained in vitro. Antimicrob Agents Chemother. 1998 Sep;42(9):2304-11. [PubMed:9736554]
  5. Varon E, Houssaye S, Grondin S, Gutmann L: Nonmolecular test for detection of low-level resistance to fluoroquinolones in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2006 Feb;50(2):572-9. [PubMed:16436712]
  6. Hombrouck C, Capmau ML, Moreau N: Overexpression, purification and photoaffinity labeling with a 3H-analogue of norfloxacin, of the GyrA and GyrB subunits of the DNA gyrase. Cell Mol Biol (Noisy-le-grand). 1999 May;45(3):347-52. [PubMed:10386791]
  7. Hooper DC: Quinolone mode of action--new aspects. Drugs. 1993;45 Suppl 3:8-14. [PubMed:7689456]
  8. Fukuda H, Hori S, Hiramatsu K: Antibacterial activity of gatifloxacin (AM-1155, CG5501, BMS-206584), a newly developed fluoroquinolone, against sequentially acquired quinolone-resistant mutants and the norA transformant of Staphylococcus aureus. Antimicrob Agents Chemother. 1998 Aug;42(8):1917-22. [PubMed:9687384]
  9. Drlica K, Zhao X: DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. [PubMed:9293187]
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]
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Magnesium ion binding
Specific Function
Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introdu...
Gene Name
topA
Uniprot ID
Q06AK7
Uniprot Name
DNA topoisomerase 1
Molecular Weight
79099.16 Da
References
  1. Tabary X, Moreau N, Dureuil C, Le Goffic F: Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and clorobiocin on Escherichia coli topoisomerase I. Antimicrob Agents Chemother. 1987 Dec;31(12):1925-8. [PubMed:2830840]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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]
  2. Fuhr U, Anders EM, Mahr G, Sorgel F, Staib AH: Inhibitory potency of quinolone antibacterial agents against cytochrome P450IA2 activity in vivo and in vitro. Antimicrob Agents Chemother. 1992 May;36(5):942-8. [PubMed:1510417]
  3. Kinzig-Schippers M, Fuhr U, Zaigler M, Dammeyer J, Rusing G, Labedzki A, Bulitta J, Sorgel F: Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2. Clin Pharmacol Ther. 1999 Mar;65(3):262-74. doi: 10.1016/S0009-9236(99)70105-0. [PubMed:10096258]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 04:59