NITROFURANTOIN

First approved in 1953

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H6N4O5
Molecular Weight	238.1574
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cc(N(=O)=O)oc1/C(/[H])=N/N2CC(=NC2=O)O

InChI

InChIKey=NXFQHRVNIOXGAQ-YCRREMRBSA-N

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+

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/009175s036lbl.pdf

Furadantin (nitrofurantoin), a synthetic chemical, is a stable, yellow, crystalline compound. Furadantin is an antibacterial agent for specific urinary tract infections. Orally administered Furadantin is readily absorbed and rapidly excreted in urine. Blood concentrations at therapeutic dosage are usually low. Unlike many drugs, the presence of food or agents delaying gastric emptying can increase the bioavailability of Furadantin, presumably by allowing better dissolution in gastric juices. 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. 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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Probable pyruvate-flavodoxin oxidoreductase 3 Target ID: P52647 Gene ID: 946587.0 Gene Symbol: ydbK Target Organism: Escherichia coli (strain K12) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12069963	Substrate 609
DNA 232 Target ID: CHEMBL2364041 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/009175s036lbl.pdf	Inhibitor 7728

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 197 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/009175s036lbl.pdf	Curative		Approved 8043	FURADANTIN Approved Use Nitrofurantoin macrocrystals is specifically indicated for the treatment of urinary tract infections when due to susceptible strains of Escherichia coli, enterococci, Staphylococcus aureus, and certain susceptible strains of Klebsiella and Enterobacter species. Nitrofurantoin is not indicated for the treatment of pyelonephritis or perinephric abscesses. To reduce the development of drug-resistant bacteria and maintain the effectiveness of nitrofurantoin macrocrystals and other antibacterial drugs, nitrofurantoin macrocrystals should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Nitrofurantoins lack the broader tissue distribution of other therapeutic agents approved for urinary tract infections. Consequently, many patients who are treated with nitrofurantoin macrocrystals are predisposed to persistence or reappearance of bacteriuria. Urine specimens for culture and susceptibility testing should be obtained before and after completion of therapy. If persistence or reappearance of bacteriuria occurs after treatment with nitrofurantoin macrocrystals, other therapeutic agents with broader tissue distribution should be selected. In considering the use of nitrofurantoin macrocrystals, lower eradication rates should be balanced against the increased potential for systemic toxicity and for the development of antimicrobial resistance when agents with broader tissue distribution are utilized. Launch Date -5.33347205E11

C_max

Value	Dose	Co-administered	Analyte	Population
0.326 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30859184	50 mg 4 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NITROFURANTOIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
0.69 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30859184	100 mg 3 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NITROFURANTOIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4.43 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30859184	50 mg 4 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NITROFURANTOIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
6.49 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30859184	100 mg 3 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NITROFURANTOIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30859184	50 mg 4 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NITROFURANTOIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30859184	100 mg 3 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NITROFURANTOIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7085535	unknown, unknown		NITROFURANTOIN plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16718946/	healthy, 50 years n = 1 Health Status: healthy Age Group: 50 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/16718946/	Disc. AE: Pneumonia... AEs leading to discontinuation/dose reduction: Pneumonia Sources: https://pubmed.ncbi.nlm.nih.gov/16718946/
125 mg multiple, oral (mean) Recommended Dose: 125 mg Route: oral Route: multiple Dose: 125 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5700010/	unhealthy, 62-75 years n = 5 Health Status: unhealthy Condition: urinary infections Age Group: 62-75 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/5700010/	Disc. AE: Interstitial pneumonitis... AEs leading to discontinuation/dose reduction: Interstitial pneumonitis Sources: https://pubmed.ncbi.nlm.nih.gov/5700010/
50 mg 2 times / day multiple, oral Studied dose Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7019458/	unhealthy, mean age 31.3 years n = 48 Health Status: unhealthy Condition: urinary infections Age Group: mean age 31.3 years Sex: F Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/7019458/	Disc. AE: Nausea... AEs leading to discontinuation/dose reduction: Nausea (28%) Sources: https://pubmed.ncbi.nlm.nih.gov/7019458/

AEs

AE	Significance	Dose	Population
Pneumonia	Disc. AE	100 mg 1 times / day multiple, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16718946/	healthy, 50 years n = 1 Health Status: healthy Age Group: 50 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/16718946/
Interstitial pneumonitis	Disc. AE	125 mg multiple, oral (mean) Recommended Dose: 125 mg Route: oral Route: multiple Dose: 125 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5700010/	unhealthy, 62-75 years n = 5 Health Status: unhealthy Condition: urinary infections Age Group: 62-75 years Sex: M+F Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/5700010/
Nausea	28% Disc. AE	50 mg 2 times / day multiple, oral Studied dose Dose: 50 mg, 2 times / day Route: oral Route: multiple Dose: 50 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7019458/	unhealthy, mean age 31.3 years n = 48 Health Status: unhealthy Condition: urinary infections Age Group: mean age 31.3 years Sex: F Population Size: 48 Sources: https://pubmed.ncbi.nlm.nih.gov/7019458/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:71415	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:71415
MolPort	MolPort-001-018-217	https://www.molport.com/shop/molecule-link/MolPort-001-018-217
ZINC	ZINC000003875368	http://zinc15.docking.org/substances/ZINC000003875368
eMolecules	886566	https://www.emolecules.com/cgi-bin/more?vid=886566

PubMed

Title	Date	PubMed
[Toxic polyneuritis in a female patient with chronic pyelonephritis after long-term treatment with nitrofurantoin].	1966 Dec 8	5980645
[Nil nocere. Severe polyneuropathy during nitrofurantoin therapy of renal insufficiency].	1968 Mar 14	5682390
[Peculiarities of nitrofurantoin polyneuropathy].	1971 Apr 30	5574121
Furadantin neuropathy.	1971 Aug	4331903
[Characteristics of nitrofurantoin-induced polyneuropathy].	1973	4727524
Nitrofurantoin polyneuropathy.	1973 May	4349239
[Polyneuropathy due to nitrofurantoin].	1975	1196664
Cholestatic hepatitis after administration of furan derivatives.	1975 May	150825
The clinical significant of cystitis cystica in girls: results of a prospective study.	1978 May	660739
Nitrofurantoin-induced granulomatous hepatitis.	1981 Aug	7269024
Nitrofurantoin neuropathy.	1981 Aug	6272676
Lateral rectus muscle palsy associated with nitrofurantoin (Macrodantin)	1982 Dec	7180920
Activation of misonidazole by rat liver microsomes and purified NADPH-cytochrome c reductase.	1982 Feb 15	6802140
Enhancement by electron-affinic agents of the therapeutic effects of cytotoxic agents against the KHT tumor: structure-activity relationships.	1982 Mar-Apr	7107385
Nitrofurantoin unmasking peripheral neuropathy in a type 2 diabetic patient.	1984 Apr	6712378
Nitrofurantoin-induced cholestatic hepatitis from cow's milk in a teenaged boy.	1984 Feb	6730475
The effect of nitrofurantoin on bladder tumor cell lines: in vitro growth and implantation in the cauterized mouse bladder.	1985 Dec	4057424
[Chronic active hepatitis caused by nitrofurantoin: a case report].	1985 Jan 26	3969597
Glutathione-dependent detoxification of peroxide in bovine ciliary body.	1990 Jun	2373173
Nitrofurantoin-induced pulmonary toxicity. In vivo evidence for oxidative stress-mediated mechanisms.	1992 Mar 3	1313237
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
Bactericidal activity of nitrofurans against growing and dormant Mycobacterium bovis BCG.	2000 Dec	11102410
Ocular myasthenia and nitrofurantoin.	2000 Oct	11024434
Activation of transcription factors by drugs inducing oxidative stress in rat liver.	2002 Jan 15	11841787
Nitrofurantoin-induced chronic active hepatitis.	2002 Mar	11908259
[Liver cirrhosis due to chronic use of nitrofurantoin].	2004 Jan 31	14983581
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Inducers of oxidative stress block ciliary neurotrophic factor activation of Jak/STAT signaling in neurons.	2005 Mar	15748169
Sex-dependent expression and activity of the ATP-binding cassette transporter breast cancer resistance protein (BCRP/ABCG2) in liver.	2005 May	15722455
Accidental intravenous administration of racemic adrenaline: two cases associated with adverse cardiac effects.	2005 Oct	16175059
Breast cancer resistance protein 1 limits fetal distribution of nitrofurantoin in the pregnant mouse.	2007 Dec	17785426
Effects of the flavonoid chrysin on nitrofurantoin pharmacokinetics in rats: potential involvement of ABCG2.	2007 Feb	17093006
Drug-induced interstitial pneumonia.	2008 Apr	18516814
Nitrofurantoin-induced peripheral neuropathy: a lesson to be re-learnt.	2008 Jan-Mar	18310854
Role of cytochrome P450 reductase in nitrofurantoin-induced redox cycling and cytotoxicity.	2008 Mar 15	18206659
Nitroreductive metabolic activation of some carcinogenic nitro heterocyclic food contaminants in rat mammary tissue cellular fractions.	2009 Jan	19017535
Knocking down breast cancer resistance protein (Bcrp) by adenoviral vector-mediated RNA interference (RNAi) in sandwich-cultured rat hepatocytes: a novel tool to assess the contribution of Bcrp to drug biliary excretion.	2009 Jan-Feb	19105722
Dequalinium, a new inhibitor of Mycobacterium tuberculosis mycothiol ligase identified by high-throughput screening.	2009 Jul	19525487
Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database.	2009 Nov 9	19761811
Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones.	2009 Oct	19754918
Acute renal failure from nitrofurantoin-induced acute granulomatous interstitial nephritis.	2010 Jan	19828642
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).	2013 Dec	24014644
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014 Jan	24085192
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541
Chemical structure-related mechanisms underlying in vivo genotoxicity induced by nitrofurantoin and its constituent moieties in gpt delta rats.	2015 May 4	25772432

Patents

Sample Use Guides

In Vivo Use Guide

Adults: 50-100 mg four times a day -- the lower dosage level is recommended for uncomplicated urinary tract infections. Pediatric Patients: 5-7 mg/kg of body weight per 24 hours, given in four divided doses (contraindicated under one month of age).

Route of Administration: Oral

In Vitro Use Guide

In vitro nitrofurantoin has the best sensitivity in community-acquired urinary tract infections (UTIs). Nitrofurantoin has showed a low MIC distribution and high sensitivity percentage (93.3%)

Name

Type

Language

NITROFURANTOIN

Official Name

English

MACROBID COMPONENT NITROFURANTOIN, MACROCRYSTALLINE

Common Name

English

NITROFURANTOIN [IARC]

Common Name

English

NITROFURANTOIN [USP]

Common Name

English

NITROFURANTOIN [INN]

Common Name

English

NITROFURANTOIN MACROCRYSTALLINE [VANDF]

Common Name

English

NITROFURANTOIN [MART.]

Common Name

English

NITROFURANTOIN [USP-RS]

Common Name

English

NSC-44150

Code

English

NITROFURANTOIN, MACROCRYSTALLINE COMPONENT OF MACROBID

Common Name

English

NITROFURANTOIN [WHO-DD]

Common Name

English

NITROFURANTOINUM ANHYDROUS [WHO-IP LATIN]

Common Name

English

FURADANTIN

Brand Name

English

NITROFURANTOIN MACROCRYSTALLINE

Common Name

English

NITROFURANTOIN ANHYDROUS [WHO-IP]

Common Name

English

NITROFURANTOIN [ORANGE BOOK]

Common Name

English

NITROFURANTOIN [VANDF]

Common Name

English

NITROFURANTOIN [GREEN BOOK]

Common Name

English

FURALAN

Brand Name

English

NITROFURANTOIN COMPONENT OF MACROBID

Common Name

English

1-((5-NITROFURFURYLIDENE)AMINO)HYDANTOIN

Systematic Name

English

1-((5-NITRO-2-FURANYL)METHYLENE)AMINO-2,4-IMIDAZOLIDENEDIONE

Common Name

English

NITROFURANTOIN [HSDB]

Common Name

English

NITROFURANTOIN ANHYDROUS

Common Name

English

NSC-2107

Code

English

NITROFURANTOIN [EP MONOGRAPH]

Common Name

English

MACRODANTIN

Brand Name

English

MACROBID COMPONENT NITROFURANTOIN

Common Name

English

NITROFURANTOIN [MI]

Common Name

English

NITROFURANTOIN [JAN]

Common Name

English

Classification Tree Code System Code

LIVERTOX

690