SULFADIAZINE

First approved in 1941

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 8297	21.0 µM [IC50]
Toxoplasma gondii 10 Target ID: CHEMBL612888 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18563892	Inhibitor 8297	41.2 µM [IC50]
Escherichia coli 82 Target ID: CHEMBL354 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17719222	Inhibitor 8297
Dihydropteroate synthetase 10 Target ID: CHEMBL2013 Sources: http://www.drugbank.ca/drugs/DB00359	Inhibitor 8297
Bacterial dihydropteroate synthase 44 Target ID: CHEMBL2364668 Sources: http://www.genome.jp/dbget-bin/www_bget?D00587	Inhibitor 8297	4.2 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Toxoplasmosis encephalitis 3 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Approved 8429	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 1994
Urinary tract infections 205 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Approved 8429	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 1994
Malaria 95 Sources: https://www.drugs.com/pro/sulfadiazine.html	Curative	Approved 8429	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 1994

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 1737	substrate 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT3 642	CYP2C8 693 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29307856/	yes [IC50 6.65 uM]

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843491/	unlikely
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26721703/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843491/	yes
P-gp 1537	substrate 3367 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
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
Flamazine is not a debriding agent.	2001 Aug 9-Sep 12	11942317
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
Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice.	2001 Dec	11718984
Development of an artificial dermis preparation capable of silver sulfadiazine release.	2001 Dec 5	11523029
An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns.	2001 Feb	11164668
The effects of octylcyanoacrylate on scarring after burns.	2001 Feb	11157284
In vitro quantitative analysis of (3)H-uracil incorporation by Sarcocytis neurona to determine efficacy of anti-protozoal agents.	2001 Feb 26	11223204
Soft tissue reconstruction for calcaneal fractures or osteomyelitis.	2001 Jan	11465125
Systematic review of antimicrobial agents used for chronic wounds.	2001 Jan	11136304
Toxoplasmosis, a severe complication in allogeneic hematopoietic stem cell transplantation: successful treatment strategies during a 5-year single-center experience.	2001 Jan	11118397
Treatment of dogs infected with Hepatozoon americanum: 53 cases (1989-1998).	2001 Jan 1	11149719
Ocular and encephalic toxoplasmosis in canaries.	2001 Jan-Mar	11332494
Antimicrobial susceptibility of starter culture bacteria used in Norwegian dairy products.	2001 Jul 20	11482563
Preparation of collagen modified hyaluronan microparticles as antibiotics carrier.	2001 Jun	11456394
Resolution of microsporidial keratoconjunctivitis in an AIDS patient treated with highly active antiretroviral therapy.	2001 Mar	11239874
Morphine-Infused silver sulfadiazine (MISS) cream for burn analgesia: a pilot study.	2001 Mar-Apr	11302598
Inhibition of aerobic growth and nitrification of bacteria in sewage sludge by antibacterial agents.	2001 May	11525487
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
A novel kind of antitumour drugs using sulfonamide as parent compound.	2001 Nov-Dec	11755229
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
[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
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
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
[Treatment of subclinical congenital toxoplasmosis by sulfadiazine and pyrimethamine continuously during 1 year: apropos of 46 cases].	2002 Jan	11865553
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
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
Iminodibenzyl as a novel coupling agent for the spectrophotometric determination of sulfonamide derivatives.	2002 Mar	11880002
[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
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
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