SULFADIAZINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H10N4O2S
Molecular Weight	250.2785
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

c1cnc(nc1)NS(=O)(=O)c2ccc(cc2)N

InChI

InChIKey=SEEPANYCNGTZFQ-UHFFFAOYSA-N

InChI=1S/C10H10N4O2S/c11-8-2-4-9(5-3-8)17(15,16)14-10-12-6-1-7-13-10/h1-7H,11H2,(H,12,13,14)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00359
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/dosage/sulfadiazine.html

Sulfadiazine is a sulfonamide 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. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. Sulfadiazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid. Used for the treatment of rheumatic fever and meningococcal meningitis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase Aurora-A 32 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18457385	Inhibitor 7701		21 µM [IC50]
Toxoplasma gondii 6 Target ID: CHEMBL612888 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18563892	Inhibitor 7701	Toxoplasmosis encephalitis	41.2000000000000028 µM [IC50]
Escherichia coli 80 Target ID: CHEMBL354 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17719222	Inhibitor 7701	Urinary tract infections
Dihydropteroate synthetase 9 Target ID: CHEMBL2013 Sources: http://www.drugbank.ca/drugs/DB00359	Inhibitor 7701	Malaria
Bacterial dihydropteroate synthase 42 Target ID: CHEMBL2364668 Sources: http://www.genome.jp/dbget-bin/www_bget?D00587	Inhibitor 7701	Urinary tract infections	4.20000000000000018 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Toxoplasmosis encephalitis 3 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Toxoplasma gondii	Approved 7997	Sulfadiazine Approved Use Sulfadiazine tablets USP are indicated in the following conditions: Chancroid Trachoma Inclusion conjunctivitis Nocardiosis Urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) in the absence of obstructive uropathy or foreign bodies, when these infections are caused by susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Staphylococcus aureus, Proteus mirabilis and P. vulgaris. Sulfadiazine should be used for urinary tract infections only after use of more soluble sulfonamides has been unsuccessful. Toxoplasmosis encephalitis in patients with and without acquired immunodeficiency syndrome, as adjunctive therapy with pyrimethamine. Malaria due to chloroquine-resistant strains of Plasmodium falciparum, when used as adjunctive therapy. Prophylaxis of meningococcal meningitis when sulfonamide-sensitive group A strains are known to prevail in family groups or larger closed populations (the prophylactic usefulness of sulfonamides when group B or C infections are prevalent is not proved and may be harmful in closed population groups). Meningococcal meningitis, when the organism has been demonstrated to be susceptible. Acute otitis media due to Haemophilusinfluenzae, when used concomitantly with adequate doses of penicillin. Prophylaxis against recurrences of rheumatic fever, as an alternative to penicillin. H. influenzae meningitis, as adjunctive therapy with parental streptomycin. Launch Date 775353600000
Urinary tract infections 197 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Escherichia coli Bacterial dihydropteroate synthase	Approved 7997	Sulfadiazine Approved Use Sulfadiazine tablets USP are indicated in the following conditions: Chancroid Trachoma Inclusion conjunctivitis Nocardiosis Urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) in the absence of obstructive uropathy or foreign bodies, when these infections are caused by susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Staphylococcus aureus, Proteus mirabilis and P. vulgaris. Sulfadiazine should be used for urinary tract infections only after use of more soluble sulfonamides has been unsuccessful. Toxoplasmosis encephalitis in patients with and without acquired immunodeficiency syndrome, as adjunctive therapy with pyrimethamine. Malaria due to chloroquine-resistant strains of Plasmodium falciparum, when used as adjunctive therapy. Prophylaxis of meningococcal meningitis when sulfonamide-sensitive group A strains are known to prevail in family groups or larger closed populations (the prophylactic usefulness of sulfonamides when group B or C infections are prevalent is not proved and may be harmful in closed population groups). Meningococcal meningitis, when the organism has been demonstrated to be susceptible. Acute otitis media due to Haemophilusinfluenzae, when used concomitantly with adequate doses of penicillin. Prophylaxis against recurrences of rheumatic fever, as an alternative to penicillin. H. influenzae meningitis, as adjunctive therapy with parental streptomycin. Launch Date 775353600000
Malaria 89 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Dihydropteroate synthetase	Approved 7997	Sulfadiazine Approved Use Sulfadiazine tablets USP are indicated in the following conditions: Chancroid Trachoma Inclusion conjunctivitis Nocardiosis Urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) in the absence of obstructive uropathy or foreign bodies, when these infections are caused by susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Staphylococcus aureus, Proteus mirabilis and P. vulgaris. Sulfadiazine should be used for urinary tract infections only after use of more soluble sulfonamides has been unsuccessful. Toxoplasmosis encephalitis in patients with and without acquired immunodeficiency syndrome, as adjunctive therapy with pyrimethamine. Malaria due to chloroquine-resistant strains of Plasmodium falciparum, when used as adjunctive therapy. Prophylaxis of meningococcal meningitis when sulfonamide-sensitive group A strains are known to prevail in family groups or larger closed populations (the prophylactic usefulness of sulfonamides when group B or C infections are prevalent is not proved and may be harmful in closed population groups). Meningococcal meningitis, when the organism has been demonstrated to be susceptible. Acute otitis media due to Haemophilusinfluenzae, when used concomitantly with adequate doses of penicillin. Prophylaxis against recurrences of rheumatic fever, as an alternative to penicillin. H. influenzae meningitis, as adjunctive therapy with parental streptomycin. Launch Date 775353600000

C_max

Value	Dose	Co-administered	Analyte	Population
84.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14742225/	2 g 2 times / day steady-state, oral dose: 2 g route of administration: Oral experiment type: STEADY-STATE co-administered:		SULFADIAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1.247 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14742225/	2 g 2 times / day steady-state, oral dose: 2 g route of administration: Oral experiment type: STEADY-STATE co-administered:		SULFADIAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/14742225/	2 g 2 times / day steady-state, oral dose: 2 g route of administration: Oral experiment type: STEADY-STATE co-administered:		SULFADIAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
4 g 1 times / day steady, oral Recommended Dose: 4 g, 1 times / day Route: oral Route: steady Dose: 4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12095805	unhealthy, 16 - 80 Health Status: unhealthy Age Group: 16 - 80 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/12095805	Disc. AE: Stenocardia, Distress gastrointestinal... Other AEs: Thrombopenia, Creatinine serum increased... AEs leading to discontinuation/dose reduction: Stenocardia (grade 3, 5%) Distress gastrointestinal (grade 3, 5%) Skin rash (grade 3, 5%) Other AEs: Thrombopenia (9%) Creatinine serum increased (5%) Elevated liver enzyme levels (5%) Malaise (23%) Diarrhea (5%) Sources: https://pubmed.ncbi.nlm.nih.gov/12095805
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/25411350	unhealthy, 29.81 Health Status: unhealthy Age Group: 29.81 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/25411350	Disc. AE: Stevens Johnson syndrome, Thrombocytopenia... Other AEs: Skin rash, Neutropenia... AEs leading to discontinuation/dose reduction: Stevens Johnson syndrome (grade 3, 1.16%) Thrombocytopenia (grade 4, 25%) Major bleed (grade 4, 25%) Other AEs: Skin rash (1.16%) Neutropenia (18.75%) Febrile neutropenia (1.16%) Sources: https://pubmed.ncbi.nlm.nih.gov/25411350
6 g 1 times / day steady, oral Recommended Dose: 6 g, 1 times / day Route: oral Route: steady Dose: 6 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1428784	unhealthy, 33.8 Health Status: unhealthy Age Group: 33.8 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/1428784	Disc. AE: Skin rash, Neutropenia... AEs leading to discontinuation/dose reduction: Skin rash (grade 3, 17.24%) Neutropenia (grade 3, 3.45%) Acute renal failure (grade 3, 6.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/1428784

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1470	substrate 865

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT3 570	CYP2C8 586 P-gp 1223

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT3 572	inhibitor 2614 Sources: https://pubmed.ncbi.nlm.nih.gov/29307856/	yes [IC50 6.65 uM]

Drug as victim

Target	Modality	Activity
CYP3A4 1470	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/15843491/	unlikely
CYP2C8 586	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/26721703/	yes
CYP2C9 865	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/15843491/	yes
P-gp 1223	substrate 2752 Sources: https://link.springer.com/article/10.1007%2Fs00204-018-2209-9	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9328	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9328
MolPort	MolPort-000-629-738	https://www.molport.com/shop/molecule-link/MolPort-000-629-738
MolPort	MolPort-003-986-619	https://www.molport.com/shop/molecule-link/MolPort-003-986-619
MolPort	MolPort-028-603-008	https://www.molport.com/shop/molecule-link/MolPort-028-603-008
ZINC	ZINC000000120319	http://zinc15.docking.org/substances/ZINC000000120319

PubMed

Title	Date	PubMed
[Kidney failure caused by sulphadiazine in patients with toxoplasma encephalitis].	2000 Nov	11322040
[New trends in ocular toxoplasmosis--the review].	2001	11921736
Pharmacokinetics and bioavailability of sulfadiazine and trimethoprim (trimazin 30%) after oral administration in non-fasted young pigs.	2001 Aug	11555186
A case of vaginal argyrosis: all that glistens isn't gold.	2001 Aug	11510720
Two episodes of life-threatening anaphylaxis in the same patient to a chlorhexidine-sulphadiazine-coated central venous catheter.	2001 Aug	11493510
[Drug hypersensitivity syndrome rapidly resolving after human immunoglobulin infusion].	2001 Dec	11908145
Development of an artificial dermis preparation capable of silver sulfadiazine release.	2001 Dec 5	11523029
Matrix solid-phase dispersion extraction and high-performance liquid chromatographic determination of residual sulfonamides in chicken.	2001 Dec 7	11765084
[Secondary prevention of opportunistic infections in HIV-infected patients].	2001 Feb	11345612
Characterization of nine Pasteurella multocida isolates from avian cholera outbreaks in Indonesia.	2001 Jan-Mar	11332497
Prevalence and characteristics of Pasteurella multocida in commercial turkeys.	2001 Jan-Mar	11332480
Antimicrobial susceptibility of starter culture bacteria used in Norwegian dairy products.	2001 Jul 20	11482563
Characterization of class 1 integrons associated with R-plasmids in clinical Aeromonas salmonicida isolates from various geographical areas.	2001 Jun	11389105
Exposure to liquid sulfur mustard.	2001 Jun	11385337
Delayed primary excision and grafting of full thickness alkali burns of the hand and forearm.	2001 Jun	11348753
New technologies to prevent intravascular catheter-related bloodstream infections.	2001 Mar-Apr	11294705
Inhibition of aerobic growth and nitrification of bacteria in sewage sludge by antibacterial agents.	2001 May	11525487
In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices.	2001 May	11328769
Neisseria meningitidis with decreased susceptibility to penicillin in Ontario, Canada 1997-2000.	2001 May 1	11381628
Determination of sulfametoxazole, sulfadiazine and associated compounds in pharmaceutical preparations by capillary zone electrophoresis.	2001 May 18	11403449
Burns and injuries resulting from the use of gel candles.	2001 May-Jun	11403248
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Management of pressure ulcers.	2001 Nov	11758876
Myelitis and ascending flaccid paralysis due to congenital toxoplasmosis.	2001 Nov 15	11641828
Safety and efficacy of an improved antiseptic catheter impregnated intraluminally with chlorhexidine.	2001 Nov-Dec	11758265
In vitro and in vivo efficacy of catheters impregnated with antiseptics or antibiotics: evaluation of the risk of bacterial resistance to the antimicrobials in the catheters.	2001 Oct	11776351
Crystalluria with sulphadiazine.	2001 Oct	11596582
Myth: silver sulfadiazine is the best treatment for minor burns.	2001 Sep	11527855
Suspected protozoal myeloencephalitis in a two-month-old colt.	2001 Sep 1	11558662
Phase II study assessing the effectiveness of Biafine cream as a prophylactic agent for radiation-induced acute skin toxicity to the breast in women undergoing radiotherapy with concomitant CMF chemotherapy.	2001 Sep 1	11516855
The beneficial toxicity paradox of antimicrobials in leg ulcer healing impaired by a polymicrobial flora: a proof-of-concept study.	2002	12011525
Determination of selected sulfonamide antibiotics and trimethoprim in manure by electrospray and atmospheric pressure chemical ionization tandem mass spectrometry.	2002	11921244
Quantification of veterinary antibiotics (sulfonamides and trimethoprim) in animal manure by liquid chromatography-mass spectrometry.	2002 Apr 5	12064522
Outbreak of serogroup W135 meningococcal disease after the Hajj pilgrimage, Europe, 2000.	2002 Aug	12141959
[Increased serum and urinary levels of silver during treatment with topical silver sulfadiazine].	2002 Feb	11937961
[Congenital toxoplasmosis: prevention in the pregnant woman and management of the neonate].	2002 Feb	11915504
Comparison of propolis skin cream to silver sulfadiazine: a naturopathic alternative to antibiotics in treatment of minor burns.	2002 Feb	11890438
Effects of silver sulphadiazine on the production of exoproteins by Staphylococcus aureus.	2002 Jan	11800472
Antimicrobial-impregnated central venous catheters.	2002 Jan	11791103
Evaluation of an antimicrobial-impregnated continuous ambulatory peritoneal dialysis catheter for infection control in rats.	2002 Jan	11774116
Complete osseous regeneration of a large skull defect in a patient with cutis aplasia: a conservative approach.	2002 Jul	12140410
An update on current practices in the management of ocular toxoplasmosis.	2002 Jul	12095816
The effectiveness of processed grapefruit-seed extract as an antibacterial agent: I. An in vitro agar assay.	2002 Jun	12165190
Anal canal amputation and necrosis of the anal sphinchter due to electric current injury.	2002 Jun	12137454
In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.	2002 Jun	12019133
Iminodibenzyl as a novel coupling agent for the spectrophotometric determination of sulfonamide derivatives.	2002 Mar	11880002
Control of wound infections using a bilayer chitosan wound dressing with sustainable antibiotic delivery.	2002 Mar 5	11774301
[Glanders--a potential disease for biological warfare in humans and animals].	2002 May	12170562
Folate deficiency during treatment with orally administered folic acid, sulphadiazine and pyrimethamine in a horse with suspected equine protozoal myeloencephalitis (EPM).	2002 May	12108754
Confocal laser microscopic observation of glycocalyx production by Staphylococcus aureus in vitro.	2002 May	12007722

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Toxoplasmosis

Route of Administration: Oral

In Vitro Use Guide

Sulfadiazine inhibited Pseudomonas aeruginosa with MIC 256 ug/mL

Name

Type

Language

SULFADIAZINE

Official Name

English

SULFADIAZINE [ORANGE BOOK]

Common Name

English

SDZ

Common Name

English

SULFADIAZINE COMPONENT OF SULFONAMIDES DUPLEX

Common Name

English

TRISULFAPYRIMIDINES (SULFADIAZINE) [ORANGE BOOK]

Common Name

English

SULFADIAZINE [INN]

Common Name

English

SULFADIAZINE [USP]

Common Name

English

NEOTRIZINE COMPONENT SULFADIAZINE

Common Name

English

SULFACOMBIN

Common Name

English

BENZENESULFONAMIDE, 4-AMINO-N-2-PYRIMIDINYL-

Systematic Name

English

N(SUP 1)-2-PYRIMIDINYLSULFANILAMIDE

Systematic Name

English

SULFADIAZINE COMPONENT OF LANTRISUL

Common Name

English

SULFADIAZINE [GREEN BOOK]

Common Name

English

SULFADIAZINE COMPONENT OF NEOTRIZINE

Common Name

English

SULFADIAZINE [JAN]

Common Name

English

SULFADIAZINE COMPONENT OF TRIPLE SULFOID

Common Name

English

TRIPLE SULFOID COMPONENT SULFADIAZINE

Common Name

English

SULFADIAZINE [WHO-DD]

Common Name

English

TERFONYL COMPONENT SULFADIAZINE

Common Name

English

COCO-DIAZINE

Brand Name

English

SULFADIAZINE COMPONENT OF TERFONYL

Common Name

English

SULFALOID COMPONENT SULFADIAZINE

Common Name

English

SULFADIAZINE [USP MONOGRAPH]

Common Name

English

SULFONAMIDES DUPLEX COMPONENT SULFADIAZINE

Common Name

English

SULFOSE COMPONENT SULFADIAZINE

Common Name

English

SULPHADIAZINE

Common Name

English

LANTRISUL COMPONENT SULFADIAZINE

Common Name

English

SULFADIAZINE COMPONENT OF SULFOSE

Common Name

English

SULFADIAZINE [VANDF]

Common Name

English

SULFADIAZINE COMPONENT OF SULFALOID

Common Name

English

SULFADIAZINE [MART.]

Common Name

English

SULFADIAZINE [EP MONOGRAPH]

Common Name

English

SULFADIMIDINE IMPURITY B [EP]

Common Name

English

SULFADIAZINE [USP-RS]

Common Name

English

TRISULFAPYRIMIDINES (SULFADIAZINE)

Common Name

English

SULFADIAZINE [MI]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ01EW10