NALIDIXIC ACID

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H12N2O3
Molecular Weight	232.2353
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1C=C(C(O)=O)C(=O)C2=C1N=C(C)C=C2

InChI

InChIKey=MHWLWQUZZRMNGJ-UHFFFAOYSA-N

InChI=1S/C12H12N2O3/c1-3-14-6-9(12(16)17)10(15)8-5-4-7(2)13-11(8)14/h4-6H,3H2,1-2H3,(H,16,17)

HIDE SMILES / InChI

Molecular Formula	C12H12N2O3
Molecular Weight	232.2353
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017430s032lbl.pdf
Curator's Comment: description was created based on several sources, including, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC432036/pdf/pnas00033-0067.pdf

Nalidixic acid is a quinolone antibacterial indicated for the treatment of urinary tract infections. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. It is suggested that nalidixic acid acts by inhibiting bacterial DNA gyrase.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial DNA gyrase 66 Target ID: CHEMBL2311224 Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC432036/pdf/pnas00033-0067.pdf	Inhibitor 8297		110.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 205 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017430s032lbl.pdf	Curative		Approved 8429	NEGGRAM Approved Use NegGram (nalidixic acid, USP) is indicated for the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species. Disc susceptibility testing with the 30 mcg disc should be performed prior to administration of the drug, and during treatment if clinical response warrants. Launch Date -1.83772807E11

C_max

Value	Dose	Co-administered	Analyte	Population
27.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7174858/	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		NALIDIXIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
327.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7174858/	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		NALIDIXIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7174858/	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		NALIDIXIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
28 g single, oral Overdose Dose: 28 g Route: oral Route: single Dose: 28 g Sources: https://pubmed.ncbi.nlm.nih.gov/500943/	healthy, 19 years n = 1 Health Status: healthy Condition: suicide attempt Age Group: 19 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/500943/	Disc. AE: Metabolic acidosis, Coma... AEs leading to discontinuation/dose reduction: Metabolic acidosis (1 patient) Coma (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/500943/
150 mg/kg single, oral Overdose Dose: 150 mg/kg Route: oral Route: single Dose: 150 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/	unhealthy, 6 months n = 12 Health Status: unhealthy Condition: acute bacillary dysentery Age Group: 6 months Sex: unknown Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/	Disc. AE: Vomiting, Intracranial hypertension... AEs leading to discontinuation/dose reduction: Vomiting (12 patients) Intracranial hypertension (12 patients) Convulsions (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/
1 g 4 times / day steady, oral Recommended Dose: 1 g, 4 times / day Route: oral Route: steady Dose: 1 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21879777/	unhealthy, adult Health Status: unhealthy Condition: acute bacillary dysentery Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/21879777/	Other AEs: Phototoxicity... Other AEs: Phototoxicity Sources: https://pubmed.ncbi.nlm.nih.gov/21879777/

AEs

AE	Significance	Dose	Population
Coma	1 patient Disc. AE	28 g single, oral Overdose Dose: 28 g Route: oral Route: single Dose: 28 g Sources: https://pubmed.ncbi.nlm.nih.gov/500943/	healthy, 19 years n = 1 Health Status: healthy Condition: suicide attempt Age Group: 19 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/500943/
Metabolic acidosis	1 patient Disc. AE	28 g single, oral Overdose Dose: 28 g Route: oral Route: single Dose: 28 g Sources: https://pubmed.ncbi.nlm.nih.gov/500943/	healthy, 19 years n = 1 Health Status: healthy Condition: suicide attempt Age Group: 19 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/500943/
Intracranial hypertension	12 patients Disc. AE	150 mg/kg single, oral Overdose Dose: 150 mg/kg Route: oral Route: single Dose: 150 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/	unhealthy, 6 months n = 12 Health Status: unhealthy Condition: acute bacillary dysentery Age Group: 6 months Sex: unknown Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/
Vomiting	12 patients Disc. AE	150 mg/kg single, oral Overdose Dose: 150 mg/kg Route: oral Route: single Dose: 150 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/	unhealthy, 6 months n = 12 Health Status: unhealthy Condition: acute bacillary dysentery Age Group: 6 months Sex: unknown Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/
Convulsions	2 patients Disc. AE	150 mg/kg single, oral Overdose Dose: 150 mg/kg Route: oral Route: single Dose: 150 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/	unhealthy, 6 months n = 12 Health Status: unhealthy Condition: acute bacillary dysentery Age Group: 6 months Sex: unknown Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/1972527/
Phototoxicity		1 g 4 times / day steady, oral Recommended Dose: 1 g, 4 times / day Route: oral Route: steady Dose: 1 g, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/21879777/	unhealthy, adult Health Status: unhealthy Condition: acute bacillary dysentery Age Group: adult Sex: unknown Sources: https://pubmed.ncbi.nlm.nih.gov/21879777/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 OAT1 599 OAT3 642 MRP4 204 UGT1A8 36 UGT1A10 32	OAT1 326 UGT 192

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
UGT1A10 41	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/43/6/812.full.pdf?with-ds=yes	inconclusive
UGT1A8 48	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/dmd/43/6/812.full.pdf?with-ds=yes	inconclusive
OAT3 644	inhibitor 3277 Sources: https://jpet.aspetjournals.org/content/362/3/450#T2	yes [IC50 0.3 uM]
MRP4 238	inhibitor 3277 Sources: https://jpet.aspetjournals.org/content/362/3/450#T2	yes [IC50 4.2 uM]
OAT1 603	inhibitor 3277 Sources: https://jpet.aspetjournals.org/content/362/3/450#T2	yes [IC50 78.3 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC188773/pdf/aac00039-0070.pdf#page=1 Page: 1,6	yes [Inhibition 500 uM]	no (co-administration study) Comment: no effects on theophylline pharmacokinetics were reported Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC188773/pdf/aac00039-0070.pdf#page=1 Page: 1,6

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 326	substrate 3367 Sources: https://jpet.aspetjournals.org/content/362/3/450	likely
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/3205675/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:100147	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:100147
ChemicalBook	CB1194283	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1194283
MolPort	MolPort-001-769-233	https://www.molport.com/shop/molecule-link/MolPort-001-769-233
Selleck Chemicals	Nalidixic-acid(NegGram)	http://www.selleckchem.com/products/Nalidixic-acid(NegGram).html
ZINC	ZINC000000057421	http://zinc15.docking.org/substances/ZINC000000057421
eMolecules	529362	https://www.emolecules.com/cgi-bin/more?vid=529362

PubMed

Title	Date	PubMed
[Multidrug resistance to antibacterial drugs of Salmonella enterica subsp. enterica strains isolated in Poland in the 1998-1999 period].	2001	11757401
[Activity of new fluoroquinolones against clinical isolates of Acinetobacter baumannii].	2001 Dec	11856982
Susceptibility of Arcobacter butzleri isolates to 23 antimicrobial agents.	2001 Dec	11737626
Synthesis, characterization and antitumor activity of quinolone-platinum(II) conjugates.	2001 Dec 1	11730897
Quinolones and false-positive urine screening for opiates by immunoassay technology.	2001 Dec 26	11754677
Campylobacter, Salmonella, Shigella and Escherichia coli in live and dressed poultry from metropolitan accra.	2001 Dec 4	11764888
Enterococcal urinary tract infections: eight years experience at a regional hospital in Trinidad, West Indies.	2001 Jan	11779446
Enteric fever treatment failures: a global concern.	2001 Jul-Aug	11585550
Antibiotic resistance and sero-groups of shigella among paediatric out-patients in southwest Ethiopia.	2001 Jun	12002106
[Increasing incidence and the mechanism of resistance of nalidixic acid resistant Shigella sonnei].	2001 Nov	11766375
Induction of pCW3-encoded tetracycline resistance in Clostridium perfringens involves a host-encoded factor.	2001 Nov	11735372
Susceptibility patterns of enteroaggregative Escherichia coli associated with traveller's diarrhoea: emergence of quinolone resistance.	2001 Nov	11699598
[Studies on halophilic vibrios causing a food poisoning outbreak in the city of Vladivostok].	2001 Nov-Dec	11881491
Typhoid and paratyphoid fever: a 10-year retrospective study of 41 cases in a Parisian hospital.	2001 Nov-Dec	11726293
Tropical diarrhoea: new developments in traveller's diarrhoea.	2001 Oct	11964874
Epidemiological analysis of Salmonella enteritidis isolates in Singapore.	2001 Oct	11798253
Comparison of minimum inhibitory concentration values for fluoroquinolones against Escherichia coli causing urinary tract infection in both hospitalized patients and outpatients.	2001 Oct	11744939
Bacterial aetiology and anti-microbial resistance of childhood diarrhoea in Yemen.	2001 Oct	11695731
[Comparative study of the bacteriostatic and bactericidal activity of levofloxacin against Pasteurella strains isolated from man].	2001 Oct	11692747
Antibiotic resistance in Escherichia coli isolates obtained from animals, foods and humans in Spain.	2001 Oct	11691568
Trends in quinolone susceptibility of Enterobacteriaceae among inpatients of a large university hospital: 1992-98.	2001 Oct	11683796
[The current antimicrobial resistance situation in Swiss veterinary medicine].	2001 Oct	11680911
Fluoroquinolone adverse effects and drug interactions.	2001 Oct	11642691
Association between cyclohexane resistance in Salmonella of different serovars and increased resistance to multiple antibiotics, disinfectants and dyes.	2001 Oct	11599743
Comparison of aztreonam against other antibiotics used in urinary tract infections.	2001 Oct-Dec	11873424
Epidemiology of shigellosis in Lagos, Nigeria: trends in antimicrobial resistance.	2001 Sep	11761772
Antimicrobial susceptibilities of Campylobacter strains isolated from broilers in the southern part of Japan from 1995 to 1999.	2001 Sep	11642273
Media for the isolation and enumeration of bifidobacteria in dairy products.	2001 Sep 28	11603854
In vitro antibiotic susceptibility of bacteria isolated from EUS-affected fishes in India.	2002	11967051
Incidence and molecular analysis of Vibrio cholerae associated with cholera outbreak subsequent to the super cyclone in Orissa, India.	2002 Apr	12002529
Salmonella enterica serotype Typhimurium DT104 isolated from humans, United States, 1985, 1990, and 1995.	2002 Apr	11971772
Effect of an efflux pump inhibitor on the MIC of nalidixic acid for Acinetobacter baumannii and Stenotrophomonas maltophilia clinical isolates.	2002 Apr	11909848
Identification of an immunodominant drug efflux pump in Burkholderia cepacia.	2002 Apr	11909835
Serovars of Salmonella isolated from Danish turkeys between 1995 and 2000 and their antimicrobial resistance.	2002 Apr 13	11995678
On the effect of covalently appended quinolones on termini of DNA duplexes.	2002 Apr 24	11960452
Time-dependent toxicity in the long-term inhibition assay with Vibrio fischeri.	2002 Feb	11999781
Comparative antibiotic resistance of diarrheal pathogens from Vietnam and Thailand, 1996-1999.	2002 Feb	11897070
[Evolution of susceptibility of aerobic gram-negative aerobic bacilli to quinolones and fluoroquinolones in a university hospital (1992-2000)].	2002 Feb	11873626
In vitro activity of clinafloxacin in comparison with other quinolones against Stenotrophomonas maltophilia clinical isolates in the presence and absence of reserpine.	2002 Feb	11858908
Green fluorescent protein-based biosensor for detecting SOS-inducing activity of genotoxic compounds.	2002 Jan	11733081
Febrile urinary tract infection: Escherichia coli susceptibility to oral antimicrobials.	2002 Mar	11956854
Emergence and rapid spread of tetracycline-resistant Vibrio cholerae strains, Madagascar.	2002 Mar	11927038
Inactivation of Escherichia coli O157:H7 on inoculated alfalfa seeds with ozonated water and heat treatment.	2002 Mar	11899041
Screening of antibiotic resistant inhibitors from local plant materials against two different strains of Staphylococcus aureus.	2002 Mar	11849842
Modified Pseudomonas agar: new differential medium for the detection/enumeration of Pseudomonas aeruginosa in mineral water.	2002 Mar	11777584
Comparison of aqueous commercial cleaners for effectiveness in removing Escherichia coli O157:H7 and Salmonella muenchen from the surface of apples.	2002 Mar 25	11929170
Antimicrobial susceptibility patterns of Campylobacter jejuni strains isolated from hospitalized children in Athens, Greece.	2002 May	12003974
Increasing quinolone resistance in Salmonella enterica serotype Enteritidis.	2002 May	11996688
Excess mortality associated with antimicrobial drug-resistant Salmonella typhimurium.	2002 May	11996684
Trends in fluoroquinolone (ciprofloxacin) resistance in enterobacteriaceae from bacteremias, England and Wales, 1990-1999.	2002 May	11996681

Patents

Sample Use Guides

In Vivo Use Guide

1 g administered four times daily for one or two weeks (adults), 25 mg/lb/day (55 mg/kg/day), administered in four equally divided doses (pediatric use).

Route of Administration: Oral

In Vitro Use Guide

The susceptibilities of the 15-nalidixic acid susceptible and 59 nalidixic acid-resistant isolates of P.mirabilis were tested against nalidixic acid. MIC50 values were 8 mg/L and >512 mg/L, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:23:22 UTC 2023` Edited by `admin` on `Sat Dec 16 16:23:22 UTC 2023`
Record UNII	3B91HWA56M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NALIDIXIC ACID

Official Name

English

WIN-18320

Code

English

1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID, 1-ETHYL-1,4-DIHYDRO-7-METHYL-4-OXO-

Common Name

English

NALIDIXIC ACID [VANDF]

Common Name

English

NALIDIXIC ACID [MI]

Common Name

English

NSC-82174

Code

English

NALIDIXIC ACID [JAN]

Common Name

English

NALIDIXIC ACID [HSDB]

Common Name

English

NALIDIXIC ACID [ORANGE BOOK]

Common Name

English

NALIDIXIC ACID [EP IMPURITY]

Common Name

English

WIN 18,320

Code

English

1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid

Systematic Name

English

NALIDIXATE

Common Name

English

nalidixic acid [INN]

Common Name

English

NALIDIXIC ACID [MART.]

Common Name

English

NEGGRAM

Brand Name

English

NALIDIXIC ACID [USAN]

Common Name

English

Nalidixic acid [WHO-DD]

Common Name

English

NALIDIXIC ACID [USP IMPURITY]

Common Name

English

Classification Tree Code System Code

LIVERTOX

663