SULFISOXAZOLE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C11H13N3O3S
Molecular Weight	267.304
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NOC(NS(=O)(=O)C2=CC=C(N)C=C2)=C1C

InChI

InChIKey=NHUHCSRWZMLRLA-UHFFFAOYSA-N

InChI=1S/C11H13N3O3S/c1-7-8(2)13-17-11(7)14-18(15,16)10-5-3-9(12)4-6-10/h3-6,14H,12H2,1-2H3

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eb6ea746-3228-4969-8a26-653288662fd7
Curator's Comment: description was created based on several sources, including

Sulfisoxazole is a sulfonamide antibacterial antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfisoxazole acetyl in combination with erythromycin ethylsuccinate is used for treatment of ACUTE OTITIS MEDIA in children that is caused by susceptible strains of Haemophilus influenzae. Sulfisoxazole acetyl is a prodrug of sulfisoxazole. Acetyl group is added to make the drug poorly water soluble, and is hydrolyzed in vivo to the active drug. Sulfisoxazole and its acetylated metabolites are excreted primarily by the kidneys through glomerular filtration. Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial dihydropteroate synthase 44 Target ID: CHEMBL2364668 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7486915	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Acute otitis media 28 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eb6ea746-3228-4969-8a26-653288662fd7	Curative		Approved 8429	ERYTHROMYCIN ETHYLSUCCINATE AND SULFISOXAZOLE ACETYL Approved Use For treatment of ACUTE OTITIS MEDIA in children that is caused by susceptible strains of Haemophilus influenzae. Launch Date 1988

C_max

Value	Dose	Co-administered	Analyte	Population
111.85 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3907496	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SULFISOXAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
874.15 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3907496	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SULFISOXAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.15 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3907496	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		SULFISOXAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
2 g single, intramuscular Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/5035788	healthy, 29-45 years n = 7 Health Status: healthy Age Group: 29-45 years Sex: M Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/5035788	Sources: https://pubmed.ncbi.nlm.nih.gov/5035788
2 g single, intravenous Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/5035788	healthy, 29-45 years n = 7 Health Status: healthy Age Group: 29-45 years Sex: M Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/5035788	Sources: https://pubmed.ncbi.nlm.nih.gov/5035788
2 g single, oral Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/5035788	healthy, 29-45 years n = 7 Health Status: healthy Age Group: 29-45 years Sex: M Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/5035788	Sources: https://pubmed.ncbi.nlm.nih.gov/5035788
4 g 1 times / day multiple, oral Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14880425	unhealthy, 74 years n = 1 Health Status: unhealthy Age Group: 74 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/14880425	Disc. AE: Granulocytopenia... AEs leading to discontinuation/dose reduction: Granulocytopenia Sources: https://pubmed.ncbi.nlm.nih.gov/14880425

AEs

AE	Significance	Dose	Population
Granulocytopenia	Disc. AE	4 g 1 times / day multiple, oral Dose: 4 g, 1 times / day Route: oral Route: multiple Dose: 4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14880425	unhealthy, 74 years n = 1 Health Status: unhealthy Age Group: 74 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/14880425

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 activator 80	inhibitor 1767

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/18505790/	weak
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10725317/	yes
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10725317/	yes
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10725317/	yes
CYP3A4 1925	activator 214 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664062/	yes
PXR 46	activator 214 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664062/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:102484	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:102484
ChemicalBook	CB1495500	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1495500
MolPort	MolPort-000-422-016	https://www.molport.com/shop/molecule-link/MolPort-000-422-016
Selleck Chemicals	Sulfisoxazole	http://www.selleckchem.com/products/Sulfisoxazole.html
ZINC	ZINC000096006009	http://zinc15.docking.org/substances/ZINC000096006009
eMolecules	511971	https://www.emolecules.com/cgi-bin/more?vid=511971

PubMed

Title	Date	PubMed
Tg.AC genetically altered mouse: assay working group overview of available data.	2001	11695563
Neonatal mouse model: review of methods and results.	2001	11695548
Bilirubin-albumin binding and free bilirubin.	2001 Dec	11803415
Antimicrobial susceptibility of Listeria monocytogenes isolated from meningoencephalitis in sheep.	2001 Mar	11282267
Prevalence of antimicrobial resistance in Salmonellae isolated from market-age swine.	2001 Oct	11601696
Cholera in the United States, 1995-2000: trends at the end of the twentieth century.	2001 Sep 15	11517445
Trends in antimicrobial resistance of Salmonella isolated from animals, foods of animal origin, and the environment of animal production in Canada, 1994-1997.	2001 Summer	11442347
Occurrence and characterization of resistance to extended-spectrum cephalosporins mediated by beta-lactamase CMY-2 in Salmonella isolated from food-producing animals in Canada.	2002 Jul	12146884
In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.	2002 Jun	12019133
Antimicrobial resistance in Salmonella enterica serovars Enteritidis and Typhimurium isolated from animals in Korea: comparison of phenotypic and genotypic resistance characterization.	2002 May 24	11955779
The use of sequential studies in a salmonellosis outbreak linked to continental custard cakes.	2002 Oct	12403104
Characterization of Pseudomonas aeruginosa isolates associated with mortality in broiler chicks.	2002 Oct-Dec	12495073
Diversity in antimicrobial resistance and other characteristics among Salmonella typhimurium DT104 isolates.	2002 Summer	12118515
Phenotypic and genotypic characterization of food animal isolates of Salmonella with reduced sensitivity to ciprofloxacin.	2002 Winter	12523636
The prevalence of Salmonella spp. in bovine faecal, rumen and carcass samples at a commercial abattoir.	2003	12631205
Antimicrobial resistance of bacteria isolated from dairy cow milk samples submitted for bacterial culture: 8,905 samples (1994-2001).	2003 Jun 1	12784967
Reflections on errors in neonatology: II. The "Heroic" years, 1950 to 1970.	2003 Mar	12673267
Survey of residual tetracycline antibiotics and sulfa drugs in kidneys of diseased animals in the Aichi Prefecture, Japan (1995-1999).	2003 May-Jun	12852565
The effect of pH and triethanolamine on sulfisoxazole complexation with hydroxypropyl-beta-cyclodextrin.	2003 Nov	14592694
Adenoidectomy versus chemoprophylaxis and placebo for recurrent acute otitis media in children aged under 2 years: randomised controlled trial.	2004 Feb 28	14769785
Enterotoxin-producing Escherichia coli O169:H41, United States.	2004 Mar	15109427
Effect of ibuprofen on bilirubin-albumin binding.	2004 Mar	15001951
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Determination of pKa values by capillary zone electrophoresis with a dynamic coating procedure.	2005 Nov	16342805
Simultaneous determination of 16 sulfonamides in honey by liquid chromatography/tandem mass spectrometry.	2005 Sep-Oct	16385979
Oxidation of sulfonamide antimicrobials by ferrate(VI) [Fe(VI)O4(2-)].	2006 Dec 1	17180970
Changes in antimicrobial susceptibility of Actinobacillus pleuropneumoniae isolated from pigs in Spain during the last decade.	2006 Jun 15	16431040
Determination of antimicrobials in sludge from infiltration basins at two artificial recharge plants by pressurized liquid extraction-liquid chromatography-tandem mass spectrometry.	2006 Oct 13	16822516
[Mutations of gyrA gene and parC gene in fluoroquinolone-resistant Escherichia coli isolates from sporadic diarrheal cases].	2006 Sep	17073264
Multiwalled carbon nanotubes as sorbent for on-line coupling of solid-phase extraction to high-performance liquid chromatography for simultaneous determination of 10 sulfonamides in eggs and pork.	2006 Sep 15	16820156
In-vitro antifungal activities of sulfa drugs against clinical isolates of Aspergillus and Cryptococcus species.	2007	17287722
Identification and molecular characterization of Salmonella spp. from unpasteurized orange juices and identification of new serotype Salmonella strain S. enterica serovar Tempe.	2007 Aug	17367687
Multidrug-resistant Salmonella enterica serotype Typhimurium associated with pet rodents.	2007 Jan 4	17202452
A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine.	2008 Aug	18505790
Comparison of antimicrobial resistance in Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes strains isolated from organic and conventional poultry meat.	2008 Dec	19244911
Antimicrobial resistance in Salmonella enterica subspecies enterica serovar Dublin from dairy source calves in the central San Joaquin Valley, California (1998-2002).	2008 Jul	18599857
Antimicrobial susceptibility profiles of Salmonella enterica serotypes recovered from pens of commercial feedlot cattle using different types of composite samples.	2009 Apr	19219500
Antimicrobial resistance pattern of Salmonella serotypes isolated from food items and personnel in Addis Ababa, Ethiopia.	2009 Feb	18516698
Genotype, serotype, and antibiotic resistance of sorbitol-negative Escherichia coli isolates from feedlot cattle.	2009 Jan	19205460
Human metapneumovirus: an emerging respiratory pathogen.	2010 May	18584996

Patents

Sample Use Guides

In Vivo Use Guide

Sulfisoxazole acetyl for oral suspension can be calculated based on the sulfisoxazole component (150 mg/kg/day to a maximum of 6 g/day). The total daily dose of sulfisoxazole acetyl for oral suspension should be administered in equally divided doses three or four times a day for 10 days

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

SULFISOXAZOLE

Common Name

English

SULFAFURAZOLE

Official Name

English

N(SUP 1)-(3,4-DIMETHYL-5-ISOXAZOLYL)SULFANILAMIDE

Systematic Name

English

SULFAFURAZOLE [MART.]

Common Name

English

SULFISOXAZOLE [VANDF]

Common Name

English

SULPHAFURAZOLE

Common Name

English

SULFISOXAZOLE [ORANGE BOOK]

Common Name

English

SULFISOXAZOLE [MI]

Common Name

English

sulfafurazole [INN]

Common Name

English

SULFISOXAZOLE [USP-RS]

Common Name

English

SULFISOXAZOLE [HSDB]

Common Name

English

SULFISOXAZOLE [USP MONOGRAPH]

Common Name

English

NSC-13120

Code

English

SULFAFURAZOLE [EP MONOGRAPH]

Common Name

English

SULFAFURAZOLE [IARC]

Common Name

English

SULFISOXAZOLE [JAN]

Common Name

English

Sulfafurazole [WHO-DD]

Common Name

English

SULFISOXAZOLE [GREEN BOOK]

Common Name

English

AZO GANTRISIN COMPONENT SULFISOXAZOLE

Common Name

English

NSC-683536

Code

English

BENZENESULFONAMIDE, 4-AMINO-N-(3,4-DIMETHYL-5-ISOXAZOLYL)-

Systematic Name

English

GANTRISIN

Brand Name

English

SULFISOXAZOLE COMPONENT OF AZO GANTRISIN

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175504