DrugBank: Nitrofurantoin (DB00698)

targets (3) enzymes (1) transporters (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

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

Brand name 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

Amerisource Health Services Corp.
Apotheca Inc.
A-S Medication Solutions LLC
Bryant Ranch Prepack
Buffalo Molasses LLC
Caremark LLC
Central Texas Community Health Centers
Comprehensive Consultant Services Inc.
Direct Dispensing Inc.
Direct Pharmaceuticals Inc.
Dispensing Solutions
Diversified Healthcare Services Inc.
Eon Labs
Gallipot
Goldline Laboratories Inc.
H.J. Harkins Co. Inc.
Heartland Repack Services LLC
Ivax Pharmaceuticals
Kaiser Foundation Hospital
Liberty Pharmaceuticals
Medvantx Inc.
Murfreesboro Pharmaceutical Nursing Supply
Mylan
Norwich Pharmaceuticals Inc.
Nucare Pharmaceuticals Inc.
Palmetto Pharmaceuticals Inc.
Patient First Corp.
PCA LLC
PD-Rx Pharmaceuticals Inc.
Pharmaceutical Utilization Management Program VA Inc.
Pharmacy Service Center
Pharmedix
Pharmpak Inc.
Physicians Total Care Inc.
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Promex Medical Inc.
Ranbaxy Laboratories
Rebel Distributors Corp.
Redpharm Drug
Remedy Repack
Sandhills Packaging Inc.
Sciele Pharma Inc.
Scruggs Pharmacal Co. Inc.
Shionogi Pharma Inc.
Southwood Pharmaceuticals
Teva Pharmaceutical Industries Ltd.
Tya Pharmaceuticals
UDL Laboratories
United Research Laboratories Inc.
Vangard Labs Inc.
Warner Chilcott Co. Inc.
Watson Pharmaceuticals
WC Pharmaceuticals

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

Patents

Not Available

Properties

State

solid

Melting point

263 oC

Experimental Properties

Property	Value	Source
water solubility	79.5 mg/L	PhysProp
logP	-0.1	PhysProp
pKa	7.2	Various sources

Predicted Properties

Property	Value	Source
water solubility	4.15e-01 g/l	ALOGPS
logP	0.03	ALOGPS
logP	-0.22	ChemAxon Molconvert
logS	-2.76	ALOGPS
pKa	14.89	ChemAxon Molconvert
hydrogen acceptor count	5	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	120.73	ChemAxon Molconvert
rotatable bond count	3	ChemAxon Molconvert
refractivity	53.11	ChemAxon Molconvert
polarizability	19.75	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00439
PubChem Compound	5353830
PubChem Substance	46504447
ChemSpider	4510228
Therapeutic Targets Database	DAP000998
PharmGKB	PA450640
Drug Product Database	319511
RxList	http://www.rxlist.com/cgi/generic/nitro25m.htm
Drugs.com	http://www.drugs.com/nitrofurantoin.html
Wikipedia	http://en.wikipedia.org/wiki/Nitrofurantoin

ATC Codes

J01XE01

AHFS Codes

08:36.00

PDB Entries

1P87

FDA label

show (922.7 KB)

MSDS

show (73.6 KB)

Interactions

Drug Interactions

Drug	Interaction

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 Gene: ydbK Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 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 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 Gene: nfsA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 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 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 Gene: rpsJ Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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

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:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
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
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:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
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
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:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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 Gene: POR Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

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

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 Gene: ABCG2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

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:

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 August 11, 2011 11:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.