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Identification
Name Nitrofurantoin
Accession Number DB00698 (APRD00191)
Type small molecule
Groups approved
Description

A bacteriostatic or bactericidal agent depending on the concentration and susceptibility of the infecting organism. Nitrofurantoin is active against some gram positive organisms such as S. aureus, S. epidermidis, S. saprophyticus, Enterococcus faecalis, S. agalactiae, group D streptococci, viridians streptococci and Corynebacterium. Its spectrum of activity against gram negative organisms includes E. coli, Enterobacter, Neisseria, Salmonella and Shigella. It may be used as an alternative to trimethoprim/sulfamethoxazole for treating urinary tract infections though it may be less effective at eradicating vaginal bacteria. May also be used in females as prophylaxis against recurrent cystitis related to coitus. Nitrofurantoin is highly stable to the development of bacterial resistance, a property thought to be due to its multiplicity of mechanisms of action.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Alfuran
Apo-Nitrofurantoin
Benkfuran
Berkfurin
Ceduran
Chemiofuran
Cistofuran
Cyantin
Cystit
Dantafur
Fua Med
Fuamed
Fur-Ren
Furabid
Furachel
Furadantin
Furadantin Retard
Furadantina MC
Furadantine
Furadantine Mc
Furadantine-Mc
Furadantoin
Furadoin
Furadoine
Furadonin
Furadonine
Furadontin
Furalan
Furaloid
Furan
Furanite
Furantoin
Furantoina
Furatoin
Furedan
Furina
Furobactina
Furophen T
Furophen T-Caps
Gerofuran
It-Uran
Ituran
Ivadantin
Macpac
Macrobid
Macrodantin
Macrodantina
Macrofuran
Macrofurin
N-Toin
Nierofu
Nifurantin
Nitoin
Nitrex
Nitrofan
Nitrofur-C
Nitrofuradantin
Novo-Furantoin
Novofuran
Orafuran
Parfuran
Phenurin
Ro-Antoin
Siraliden
Trantoin
Uerineks
Upiol
Urantoin
Urizept
Uro-Selz
Uro-Tablinen
Urodin
Urofuran
Urofurin
Urolisa
Urolong
USAF EA-2
Uvaleral
Welfurin
Zoofurin
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Brand mixtures Not Available
Categories
  • Anti-Infectives
  • Anti-Infective Agents, Urinary
CAS number 67-20-9
Weight Average: 238.157
Monoisotopic: 238.033819322
Chemical Formula C8H6N4O5
InChI Key InChIKey=NXFQHRVNIOXGAQ-OQFOIZHKSA-N
InChI
InChI=1S/C8H6N4O5/c13-6-4-11(8(14)10-6)9-3-5-1-2-7(17-5)12(15)16/h1-3H,4H2,(H,10,13,14)/b9-3-
Plain Text
IUPAC Name
1-[(Z)-[(5-nitrofuran-2-yl)methylidene]amino]imidazolidine-2,4-dione
SMILES
[O-][N+](=O)C1=CC=C(O1)\C=N/N1CC(=O)NC1=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Nitrofurans
  • Imidazolidines
Substructures
  • Semicarbazones
  • Carboxylic Acids and Derivatives
  • Oxoazaniums
  • Amino Ketones
  • Nitro compounds
  • Nitrofurans
  • Imidazolidines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Semicarbazides
  • Hydrazine Derivatives
  • Furans
  • Imines
Pharmacology
Indication May be used as an alternative in the treatment of urinary tract infections. May be used by females pericoitally for prophylaxis against recurrent cystitis related to coitus.
Pharmacodynamics Nitrofurantoin exhibits bacteriostatic or bactericidal effects by inhibiting the synthesis of DNA, RNA, protein and cell wall synthesis.
Mechanism of action Nitrofurantoin is activated by bacterial flavoproteins (nitrofuran reductase) to active reduced reactive intermediates that are thought to modulate and damage ribosomal proteins or other macromolecules, especially DNA, causing inhibition of DNA, RNA, protein, and cell wall synthesis. The overall effect is inhibition of bacterial growth or cell death.
Absorption Readily absorbed in GI tract primarily in small intestine. Enhanced by food or delayed gastric emptying via enhanced dissolution rate of the drug.
Volume of distribution Not Available
Protein binding 20-60% bound to plasma proteins
Metabolism Partially metabolized in liver to aminofurantoin.
Route of elimination Not Available
Half life 0.3-1 hour
Clearance Not Available
Toxicity Acute toxicity may cause vomiting. Adverse effects include nausea and urine discolouration. Rare hepatotoxic and hypersensitivity reactions have occurred. Hemolytic anemia is a risk in patients with G6PD deficiency. Ascending polyneuropathy may occur with prolonged therapy or in patients with low creatinine clearance.
Affected organisms
  • Gram negative and gram positive bacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Watson laboratories inc
  • Shionogi pharma inc
  • Procter and gamble pharmaceuticals inc sub procter and gamble co
  • Lannett co inc
  • Elkins sinn div ah robins co inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sandoz inc
  • Whiteworth towne paulsen inc
  • Alvogen inc
  • Mylan pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Tablet Oral
Prices
Unit description Cost Unit
Macrobid 100 mg capsule 3.02 USD capsule
Macrodantin 100 mg capsule 2.67 USD capsule
Furadantin 25 mg/5ml Suspension 2.22 USD ml
Furadantin 25 mg/5 ml susp 2.13 USD ml
Nitrofurantoin powder 2.13 USD g
Nitrofurantoin Monohyd Macro 100 mg capsule 2.12 USD capsule
Nitrofurantoin mono-mcr 100 mg 2.04 USD each
Nitrofurantoin-macro 100 mg 2.04 USD each
Nitrofurantoin Macrocrystal 100 mg capsule 1.88 USD capsule
Nitrofurantoin mcr 100 mg capsule 1.86 USD capsule
Macrodantin 50 mg capsule 1.67 USD capsule
Macrodantin 25 mg capsule 1.3 USD capsule
Nitrofurantoin Macrocrystal 50 mg capsule 1.14 USD capsule
Nitrofurantoin mcr 50 mg capsule 1.09 USD capsule
Macrobid 100 mg Capsule (Macrocrystals/Monohydrate) 0.78 USD capsule
Novo-Furantoin 100 mg Capsule (Macrocrystals) 0.66 USD capsule
Novo-Furantoin 50 mg Capsule (Macrocrystals) 0.35 USD capsule
Apo-Nitrofurantoin 100 mg Tablet 0.23 USD tablet
Apo-Nitrofurantoin 50 mg Tablet 0.17 USD tablet
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 263 °C PhysProp
water solubility 79.5 mg/L (at 24 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP -0.47 HANSCH,C ET AL. (1995)
pKa 7.2 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 4.15e-01 g/l ALOGPS
logP 0.03 ALOGPS
logP -0.22 ChemAxon
logS -2.8 ALOGPS
pKa (strongest acidic) 9.23 ChemAxon
pKa (strongest basic) -2.2 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 120.73 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 53.11 ChemAxon
polarizability 19.75 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00439 Link_out
PubChem Compound 5353830 Link_out
PubChem Substance 46504447 Link_out
ChemSpider 4510228 Link_out
Therapeutic Targets Database DAP000998 Link_out
PharmGKB PA450640 Link_out
Drug Product Database 319511 Link_out
RxList http://www.rxlist.com/cgi/generic/nitro25m.htm Link_out
Drugs.com http://www.drugs.com/nitrofurantoin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Nitrofurantoin Link_out
ATC Codes
  • J01XE01
AHFS Codes
  • 08:36.00
PDB Entries
FDA label show (923 KB)
MSDS show (73.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Do not take magnesium at the same time.
  • Take with food since it increases bioavailability and reduces irritation.
Targets

1. Probable pyruvate-flavodoxin oxidoreductase

Pharmacological action: yes
Actions: potentiator

Oxidoreductase required for the transfer of electrons from pyruvate to flavodoxin (Potential)

Organism class: bacterial
UniProt ID: P52647 Link_out
Gene: ydbK
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. Breeze AS, Obaseiki-Ebor EE: Nitrofuran reductase activity in nitrofurantoin-resistant strains of Escherichia coli K12: some with chromosomally determined resistance and others carrying R-plasmids. J Antimicrob Chemother. 1983 Dec;12(6):543-7. Pubmed
  4. Sisson G, Goodwin A, Raudonikiene A, Hughes NJ, Mukhopadhyay AK, Berg DE, Hoffman PS: Enzymes associated with reductive activation and action of nitazoxanide, nitrofurans, and metronidazole in Helicobacter pylori. Antimicrob Agents Chemother. 2002 Jul;46(7):2116-23. Pubmed

2. Oxygen-insensitive NADPH nitroreductase

Pharmacological action: yes
Actions: potentiator

Reduction of nitroaromatic compounds using NADH. Reduces nitrofurazone by a ping-pong bi-bi mechanism possibly to generate a two-electron transfer product. Major component of the oxygen- insensitive nitroreductase activity in E.coli

Organism class: bacterial
UniProt ID: P17117 Link_out
Gene: nfsA
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. Kutty R, Bennett GN: Biochemical characterization of trinitrotoluene transforming oxygen-insensitive nitroreductases from Clostridium acetobutylicum ATCC 824. Arch Microbiol. 2005 Nov;184(3):158-67. Epub 2005 Nov 10. Pubmed
  4. Lightfoot RT, Shuman D, Ischiropoulos H: Oxygen-insensitive nitroreductases of Escherichia coli do not reduce 3-nitrotyrosine. Free Radic Biol Med. 2000 Apr 1;28(7):1132-6. Pubmed

3. 30S ribosomal protein S10

Pharmacological action: unknown

Involved in the binding of tRNA to the ribosomes

Organism class: bacterial
UniProt ID: P0A7R5 Link_out
Gene: rpsJ
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
Enzymes

1. NADPH--cytochrome P450 reductase

Actions: substrate

This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5

UniProt ID: P16435 Link_out
Gene: POR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang Y, Gray JP, Mishin V, Heck DE, Laskin DL, Laskin JD: Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity. Free Radic Biol Med. 2008 Mar 15;44(6):1169-79. Epub 2007 Dec 23. Pubmed
Transporters

1. ATP-binding cassette sub-family G member 2

Actions: substrate

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Perez M, Real R, Mendoza G, Merino G, Prieto JG, Alvarez AI: Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones. J Vet Pharmacol Ther. 2009 Oct;32(5):498-502. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19