U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of NITROFURANTOIN

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
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

Sources: Transactions. American Urological Association. Southeastern Section (1952), 2-5, (2-5), 26-34.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P52647
Gene ID: 946587.0
Gene Symbol: ydbK
Target Organism: Escherichia coli (strain K12)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.326 mg/L
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
4.43 mg × h/L
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.3 h
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
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
10%
unknown, unknown
NITROFURANTOIN plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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:
healthy, 50 years
n = 1
Health Status: healthy
Age Group: 50 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Pneumonia...
AEs leading to
discontinuation/dose reduction:
Pneumonia
Sources:
125 mg multiple, oral (mean)
Recommended
Dose: 125 mg
Route: oral
Route: multiple
Dose: 125 mg
Sources:
unhealthy, 62-75 years
n = 5
Health Status: unhealthy
Condition: urinary infections
Age Group: 62-75 years
Sex: M+F
Population Size: 5
Sources:
Disc. AE: Interstitial pneumonitis...
AEs leading to
discontinuation/dose reduction:
Interstitial pneumonitis
Sources:
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:
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:
Disc. AE: Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (28%)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
healthy, 50 years
n = 1
Health Status: healthy
Age Group: 50 years
Sex: F
Population Size: 1
Sources:
Interstitial pneumonitis Disc. AE
125 mg multiple, oral (mean)
Recommended
Dose: 125 mg
Route: oral
Route: multiple
Dose: 125 mg
Sources:
unhealthy, 62-75 years
n = 5
Health Status: unhealthy
Condition: urinary infections
Age Group: 62-75 years
Sex: M+F
Population Size: 5
Sources:
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:
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:
PubMed

PubMed

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

Sample Use Guides

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 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
EP   GREEN BOOK   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
INN  
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
VANDF  
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
WHO-IP  
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
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
NDF-RT N0000007658
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.2.2
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
WHO-ATC J01XE01
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
IARC Nitrofurantoin
NCI_THESAURUS C255
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
NDF-RT N0000175494
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
WHO-ATC J01XE51
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
WHO-VATC QJ01XE01
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
NDF-RT N0000007658
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C29293
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
DRUG BANK
DB00698
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
ChEMBL
CHEMBL572
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
MESH
D009582
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
USP_CATALOG
1464001
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY USP-RS
DRUG CENTRAL
1949
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
NITROFURANTOIN
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY Description: Lemon-yellow crystals or a yellow, crystalline powder; odourless or almost odourless. Solubility: Practically insoluble in water; very slightly soluble in ethanol (~750 g/l) TS; soluble in dimethylformamide R. Category: Antibacterial drug. Storage: Nitrofurantoin should be kept in a well-closed container, protected from light, and stored at a temperature not exceeding25?C. Labelling: The designation on the container of Nitrofurantoin should state whether the substance is the monohydrate or is in theanhydrous form. Additional information: Nitrofurantoin melts at about 271?C with decomposition. Nitrofurantoin and its solutions are discoloured byalkali and by exposure to light and are decomposed upon contact with metals other than stainless steel and aluminium. Definition: Nitrofurantoin contains not less than 98.0% and not more than 102.0% of C8H6N4O5, calculated with reference to thedried substance.
RXCUI
7454
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
FDA UNII
927AH8112L
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
EVMPD
SUB129837
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
WIKIPEDIA
NITROFURANTOIN
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
LACTMED
Nitrofurantoin
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
MERCK INDEX
M7956
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY Merck Index
CAS
67-20-9
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
INN
488
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-646-5
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
PUBCHEM
6604200
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY
EVMPD
SUB09326MIG
Created by admin on Fri Jun 25 20:56:12 UTC 2021 , Edited by admin on Fri Jun 25 20:56:12 UTC 2021
PRIMARY