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Identification
NameNitrofurantoin
Accession NumberDB00698  (APRD00191)
TypeSmall Molecule
GroupsApproved
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
Synonyms
SynonymLanguageCode
5-NitrofurantoinNot AvailableNot Available
N-(5-Nitrofurfurylidene)-1-aminohydantoinNot AvailableNot Available
SID11112186Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
FurabidGoldshield
FuradantinGlaxoSmithKline
MacrobidAlvogen
MacrodantinGoldshield
NiftranNot Available
SiralidenNot Available
UrantoinBasel
UrolongThiemann
Brand mixturesNot Available
Categories
CAS number67-20-9
WeightAverage: 238.157
Monoisotopic: 238.033819322
Chemical FormulaC8H6N4O5
InChI KeyNXFQHRVNIOXGAQ-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-
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzolidines
SubclassImidazolidines
Direct parentHydantoins
Alternative parentsNitrofurans; Ureides; Semicarbazones; N-unsubstituted Carboxylic Acid Imides; Hydrazones; Nitronic Acids; Aldimines; Nitro Compounds; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids; Organic Oxoazanium Compounds
Substituents2-nitrofuran; ureide; semicarbazone; carboxylic acid imide, n-unsubstituted; semicarbazide; hydrazone; furan; carboxamide group; secondary carboxylic acid amide; nitro compound; nitronic acid; aldimine; organic oxoazanium; carboxylic acid derivative; carboxylic acid; polyamine; amine; imine; organonitrogen compound
Classification descriptionThis compound belongs to the hydantoins. These are heterocyclic compounds containing an imidazolidine substituted by ketone group at positions 2 and 4.
Pharmacology
IndicationMay 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.
PharmacodynamicsNitrofurantoin exhibits bacteriostatic or bactericidal effects by inhibiting the synthesis of DNA, RNA, protein and cell wall synthesis.
Mechanism of actionNitrofurantoin 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.
AbsorptionReadily absorbed in GI tract primarily in small intestine. Enhanced by food or delayed gastric emptying via enhanced dissolution rate of the drug.
Volume of distributionNot Available
Protein binding20-60% bound to plasma proteins
Metabolism

Partially metabolized in liver to aminofurantoin.

SubstrateEnzymesProduct
Nitrofurantoin
Not Available
aminofurantoinDetails
Route of eliminationNot Available
Half life0.3-1 hour
ClearanceNot Available
ToxicityAcute 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9832
Blood Brain Barrier + 0.958
Caco-2 permeable - 0.575
P-glycoprotein substrate Non-substrate 0.6374
P-glycoprotein inhibitor I Non-inhibitor 0.8661
P-glycoprotein inhibitor II Non-inhibitor 0.9834
Renal organic cation transporter Non-inhibitor 0.8835
CYP450 2C9 substrate Non-substrate 0.8373
CYP450 2D6 substrate Non-substrate 0.8757
CYP450 3A4 substrate Substrate 0.5799
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.9069
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8943
Ames test AMES toxic 0.9231
Carcinogenicity Non-carcinogens 0.8869
Biodegradation Ready biodegradable 0.7448
Rat acute toxicity 2.5717 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7981
hERG inhibition (predictor II) Non-inhibitor 0.94
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
FormRouteStrength
CapsuleOral
TabletOral
Prices
Unit descriptionCostUnit
Macrobid 100 mg capsule3.02USDcapsule
Macrodantin 100 mg capsule2.67USDcapsule
Furadantin 25 mg/5ml Suspension2.22USDml
Furadantin 25 mg/5 ml susp2.13USDml
Nitrofurantoin powder2.13USDg
Nitrofurantoin Monohyd Macro 100 mg capsule2.12USDcapsule
Nitrofurantoin mono-mcr 100 mg2.04USDeach
Nitrofurantoin-macro 100 mg2.04USDeach
Nitrofurantoin Macrocrystal 100 mg capsule1.88USDcapsule
Nitrofurantoin mcr 100 mg capsule1.86USDcapsule
Macrodantin 50 mg capsule1.67USDcapsule
Macrodantin 25 mg capsule1.3USDcapsule
Nitrofurantoin Macrocrystal 50 mg capsule1.14USDcapsule
Nitrofurantoin mcr 50 mg capsule1.09USDcapsule
Macrobid 100 mg Capsule (Macrocrystals/Monohydrate)0.78USDcapsule
Novo-Furantoin 100 mg Capsule (Macrocrystals)0.66USDcapsule
Novo-Furantoin 50 mg Capsule (Macrocrystals)0.35USDcapsule
Apo-Nitrofurantoin 100 mg Tablet0.23USDtablet
Apo-Nitrofurantoin 50 mg Tablet0.17USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point223-228Gever, G.; U.S. Patent 2,802,002; August 6, 1957; assigned to The Norwich Pharmacal Co.
water solubility79.5 mg/L (at 24 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.47HANSCH,C ET AL. (1995)
pKa7.2SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.415ALOGPS
logP0.03ALOGPS
logP-0.22ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)9.23ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area120.73 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity53.11 m3·mol-1ChemAxon
Polarizability19.75 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Tara Bielski, Kerry Benson, “Novel orally administrable formulation of nitrofurantoin and a method for preparing said formulation.” U.S. Patent US20050202079, issued September 15, 2005.

US20050202079
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00439
PubChem Compound5353830
PubChem Substance46504447
ChemSpider4510228
Therapeutic Targets DatabaseDAP000998
PharmGKBPA450640
Drug Product Database319511
RxListhttp://www.rxlist.com/cgi/generic/nitro25m.htm
Drugs.comhttp://www.drugs.com/nitrofurantoin.html
WikipediaNitrofurantoin
ATC CodesJ01XE01
AHFS Codes
  • 08:36.00
PDB Entries
FDA labelshow(923 KB)
MSDSshow(73.6 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Probable pyruvate-flavodoxin oxidoreductase

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Probable pyruvate-flavodoxin oxidoreductase P52647 Details

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

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Oxygen-insensitive NADPH nitroreductase P17117 Details

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

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: unknown

Components

Name UniProt ID Details
30S ribosomal protein S10 P0A7R5 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
NADPH--cytochrome P450 reductase P16435 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11