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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
SaltsNot Available
Brand names
NameCompany
FurabidNot Available
FuradantinNot Available
MacrobidNot Available
MacrodantinNot Available
NiftranNot Available
SiralidenNot Available
UrantoinNot Available
UrolongNot Available
Brand mixturesNot Available
Categories
CAS number67-20-9
WeightAverage: 238.157
Monoisotopic: 238.033819322
Chemical FormulaC8H6N4O5
InChI KeyInChIKey=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-
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
    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 point263 °CPhysProp
    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 solubility4.15e-01 g/lALOGPS
    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 area120.73ChemAxon
    rotatable bond count3ChemAxon
    refractivity53.11ChemAxon
    polarizability19.75ChemAxon
    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

    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

    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

    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

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