SULFADIAZINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H10N4O2S
Molecular Weight	250.277
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=CC=C(C=C1)S(=O)(=O)NC2=NC=CC=N2

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	Potency
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18457385	Inhibitor 8228	21.0 µM [IC50]
Toxoplasma gondii 10 Target ID: CHEMBL612888 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18563892	Inhibitor 8228	41.2 µM [IC50]
Escherichia coli 80 Target ID: CHEMBL354 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17719222	Inhibitor 8228
Dihydropteroate synthetase 10 Target ID: CHEMBL2013 Sources: http://www.drugbank.ca/drugs/DB00359	Inhibitor 8228
Bacterial dihydropteroate synthase 44 Target ID: CHEMBL2364668 Sources: http://www.genome.jp/dbget-bin/www_bget?D00587	Inhibitor 8228	4.2 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Toxoplasmosis encephalitis 3 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Approved 8360	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 7.753536E11
Urinary tract infections 204 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Approved 8360	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 7.753536E11
Malaria 94 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Approved 8360	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 7.753536E11

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 Co-administed with:: pyrimethamine(50 mg oral; 1/day) folinic acid(15 mg oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/12095805 Page: p.36, 38	unhealthy, 16 - 80 n = 22 Health Status: unhealthy Condition: Ocular toxoplasmosis Age Group: 16 - 80 Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/12095805 Page: p.36, 38	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 Page: p.36, 38
1 g 4 times / day steady, oral Recommended Dose: 1 g, 4 times / day Route: oral Route: steady Dose: 1 g, 4 times / day Co-administed with:: pyrimethamine(50-75 mg oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/25411350 Page: p.4	unhealthy, 29.81 n = 16 Health Status: unhealthy Condition: Cerebral toxoplasmosis Age Group: 29.81 Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/25411350 Page: p.4	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 Page: p.4
6 g 1 times / day steady, oral (max) Recommended Dose: 6 g, 1 times / day Route: oral Route: steady Dose: 6 g, 1 times / day Co-administed with:: pyrimethamine(50-75 mg oral; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/1428784 Page: p.476	unhealthy, 33.8 n = 29 Health Status: unhealthy Condition: Central nervous system toxoplasmosis Age Group: 33.8 Sex: M+F Population Size: 29 Sources: https://pubmed.ncbi.nlm.nih.gov/1428784 Page: p.476	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 Page: p.476

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	substrate 1010

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT3 636	CYP2C8 688 P-gp 1527

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT3 638	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/29307856/	yes [IC50 6.65 uM]

Drug as victim

Target	Modality	Activity
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/15843491/	unlikely
CYP2C8 688	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/26721703/	yes
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/15843491/	yes
P-gp 1527	substrate 3326 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
ChemicalBook	CB4166214	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4166214
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
Selleck Chemicals	Sulfadiazine	http://www.selleckchem.com/products/Sulfadiazine.html
ZINC	ZINC000000120319	http://zinc15.docking.org/substances/ZINC000000120319
eMolecules	474308	https://www.emolecules.com/cgi-bin/more?vid=474308

PubMed

Title	Date	PubMed
[New trends in ocular toxoplasmosis--the review].	2001	11921736
Flamazine is not a debriding agent.	2001 Aug 9-Sep 12	11942317
[Drug hypersensitivity syndrome rapidly resolving after human immunoglobulin infusion].	2001 Dec	11908145
Bullous eruptions caused by extravasation of mannitol--a case report.	2001 Dec	11840587
Efficacy of antiadhesive, antibiotic and antiseptic coatings in preventing catheter-related infections: review.	2001 Dec	11806619
Matrix solid-phase dispersion extraction and high-performance liquid chromatographic determination of residual sulfonamides in chicken.	2001 Dec 7	11765084
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Management of pressure ulcers.	2001 Nov	11758876
Safety and efficacy of an improved antiseptic catheter impregnated intraluminally with chlorhexidine.	2001 Nov-Dec	11758265
A novel kind of antitumour drugs using sulfonamide as parent compound.	2001 Nov-Dec	11755229
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
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
[A case of primary pyoderma-like aspergillosis occurring in a patient with a cervical spinal cord injury].	2002	11865295
Submaxillary adenopathy as sole manifestation of toxoplasmosis: case report and literature review.	2002 Apr	12019742
Prevalence of moderate penicillin resistant invasive Neisseria meningitidis infection in Scotland, 1994-9.	2002 Apr	12002531
Transfer and distribution profiles of dietary sulphonamides in the tissues of the laying hen.	2002 Apr	11962694
Quantification of veterinary antibiotics (sulfonamides and trimethoprim) in animal manure by liquid chromatography-mass spectrometry.	2002 Apr 5	12064522
New simple liquid chromatographic method for the determination of trimethoprim, sulfadiazine and N4-acetylsulfadiazine in plasma of broilers.	2002 Apr 5	11996491
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
Deep partial thickness burn after contact with a Meal Ready-To-Eat heater.	2002 Feb	11873544
Effect of sulphadiazine and trimethoprim on the immune response of rainbow trout (Oncorhynchus mykiss).	2002 Feb	11867171
[Treatment of subclinical congenital toxoplasmosis by sulfadiazine and pyrimethamine continuously during 1 year: apropos of 46 cases].	2002 Jan	11865553
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
Atypical anterior optic neuropathy caused by toxoplasmosis.	2002 Jan	11755864
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
A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis.	2002 Jul	12095805
An infection-preventing bilayered collagen membrane containing antibiotic-loaded hyaluronan microparticles: physical and biological properties.	2002 Jul	12081522
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
Laminin modified infection-preventing collagen membrane containing silver sulfadiazine-hyaluronan microparticles.	2002 Jun	12072108
In vitro activities of pentamidine, pyrimethamine, trimethoprim, and sulfonamides against Aspergillus species.	2002 Jun	12019133
Silver-coated endotracheal tubes associated with reduced bacterial burden in the lungs of mechanically ventilated dogs.	2002 Mar	11888974
Is a silver coating a silver lining?	2002 Mar	11888943
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
[Topical agents used in the treatment of burns].	2002 Mar-Apr	12070926
[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
Silver. 2: Toxicity in mammals and how its products aid wound repair.	2002 May	12055941
Confocal laser microscopic observation of glycocalyx production by Staphylococcus aureus in vitro.	2002 May	12007722
Unsuspected Toxoplasma gondii empyema in a bone marrow transplant recipient.	2002 May 1	11941570
Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039.	2002 May 1	11941551
Effect of sulfadiazine and pyrimethamine on selected physiologic and performance parameters in athletically conditioned thoroughbred horses during an incremental exercise stress test.	2002 Spring	12050828

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Toxoplasmosis Toxoplasmic encephalitis: Initial dose: Pyrimethamine 200 mg orally once Maintenance dose: <60 kg: Sulfadiazine 1 g orally every 6 hours plus pyrimethamine 50 mg orally once a day. >=60 kg: Sulfadiazine 1500 mg orally every 6 hours plus pyrimethamine 75 mg orally once a day. In addition, leucovorin 10 to 20 mg/day orally (may increase up to 50 mg/day).

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

NEOTRIZINE COMPONENT SULFADIAZINE

Common Name

English

SULFACOMBIN

Common Name

English

SULFADIMIDINE IMPURITY B [EP IMPURITY]

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 [USP IMPURITY]

Common Name

English

SULFADIAZINE COMPONENT OF TRIPLE SULFOID

Common Name

English

TRIPLE SULFOID COMPONENT SULFADIAZINE

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

Sulfadiazine [WHO-DD]

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