Identification

Name
Sulfadiazine
Accession Number
DB00359  (APRD00190)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

One of the short-acting sulfonamides used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. [PubChem]

Structure
Thumb
Synonyms
  • 2-sulfanilamidopyrimidine
  • 2-sulfanilylaminopyrimidine
  • 4-amino-N-2-pyrimidinylbenzenesulfonamide
  • N(1)-2-Pyrimidinylsulfanilamide
  • N(1)-2-Pyrimidylsulfanilamide
  • N1-2-pyrimidinylsulfanilamide
  • N1-2-pyrimidylsulfanilamide
  • Sulfadiazina
  • Sulfadiazine
  • Sulfadiazinum
  • Sulfapyrimidine
  • Sulphadiazine
Product Ingredients
IngredientUNIICASInChI Key
Sulfadiazine sodium84CS1P306F547-32-0JLDCNMJPBBKAHH-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sulfadiazine Tab 7.7grTablet500.5 mgOralStanley Pharmaceuticals, A Division Of Vita Health Products Inc.1957-12-312001-07-20Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SulfadiazineTablet500 mg/1OralRemedy Repack2012-09-202013-03-25Us
SulfadiazineTablet500 mg/1OralEon Labs, Inc.1994-07-29Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Coptin Oral SuspensionSulfadiazine (41 mg) + Trimethoprim (9 mg)SuspensionOralAxcan Pharma1979-12-312006-09-12Canada
Coptin TabSulfadiazine (410 mg) + Trimethoprim (90 mg)TabletOralPfizer1979-12-311996-09-09Canada
Coptin TabSulfadiazine (410 mg) + Trimethoprim (90 mg)TabletOralAxcan Pharma1979-12-312006-09-12Canada
Ovoquinol ConesSulfadiazine (400 mg) + Diiodohydroxyquinoline (75 mg) + Undecylenic acid (50 mg)SuppositoryVaginalLab Nadeau LtÉe, Division Of Technilab Inc.1963-12-311999-09-28Canada
Ovoquinol Crm VaginaleSulfadiazine (8 %) + Diiodohydroxyquinoline (2 %) + Undecylenic acid (1 %)CreamVaginalLab Nadeau LtÉe, Division Of Technilab Inc.1980-12-311999-09-28Canada
Trisulfaminic SusSulfadiazine (167 mg) + Mepyramine maleate (6.25 mg) + Pheniramine maleate (6.25 mg) + Phenylpropanolamine hydrochloride (12.5 mg) + Sulfamerazine (167 mg) + Sulfamethazine (167 mg)SuspensionOralShepherd Pharmaceuticals Inc.1959-12-312001-04-11Canada
Trisulfaminic TabSulfadiazine (167 mg) + Mepyramine maleate (6.25 mg) + Pheniramine maleate (6.25 mg) + Phenylpropanolamine hydrochloride (12.5 mg) + Sulfamerazine (167 mg) + Sulfamethazine (167 mg)TabletOralShepherd Pharmaceuticals Inc.1959-12-312001-04-11Canada
International/Other Brands
Adiazine
Categories
UNII
0N7609K889
CAS number
68-35-9
Weight
Average: 250.277
Monoisotopic: 250.052446274
Chemical Formula
C10H10N4O2S
InChI Key
SEEPANYCNGTZFQ-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-amino-N-(pyrimidin-2-yl)benzene-1-sulfonamide
SMILES
NC1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=N1

Pharmacology

Indication

For the treatment of rheumatic fever and meningococcal meningitis

Associated Conditions
Pharmacodynamics

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.

Mechanism of action

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.

TargetActionsOrganism
ADihydropteroate synthetase
inhibitor
Plasmodium falciparum
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Sulfadiazine is excreted largely in the urine.

Half life
Not Available
Clearance
Not Available
Toxicity

Oral LD50 in mouse is 1500 mg/kg.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Sulfadiazine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Sulfadiazine is combined with (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Sulfadiazine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Sulfadiazine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Sulfadiazine.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Sulfadiazine can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Sulfadiazine.
6-Deoxyerythronolide BThe metabolism of Sulfadiazine can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Sulfadiazine.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Sulfadiazine.
Food Interactions
Not Available

References

Synthesis Reference

Charles L. Fox, Jr., Shanta M. Modak, Paul Fox, "Wound dressing comprising silver sulfadiazine incorporated in animal tissue and method of preparation." U.S. Patent US4599226, issued September, 1977.

US4599226
General References
Not Available
External Links
Human Metabolome Database
HMDB0014503
KEGG Drug
D00587
KEGG Compound
C07658
PubChem Compound
5215
PubChem Substance
46506164
ChemSpider
5026
BindingDB
50166571
ChEBI
9328
ChEMBL
CHEMBL439
Therapeutic Targets Database
DAP001238
PharmGKB
PA451539
Drugs.com
Drugs.com Drug Page
Wikipedia
Sulfadiazine
ATC Codes
J01EE06 — Sulfadiazine and tetroxoprimG01AE10 — Combinations of sulfonamidesJ01EC02 — SulfadiazineJ01EE02 — Sulfadiazine and trimethoprim
MSDS
Download (73.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
2CompletedTreatmentMinor burns1
3CompletedTreatmentToxoplasmosis, Congenital1
4RecruitingTreatmentToxoplasmosis1

Pharmacoeconomics

Manufacturers
  • Abbott laboratories pharmaceutical products div
  • Everylife
  • Impax laboratories inc
  • Lannett co inc
  • Lederle laboratories div american cyanamid co
  • Eli lilly and co
  • Sandoz inc
Packagers
  • Amend
  • A-S Medication Solutions LLC
  • C.O. Truxton Inc.
  • Eon Labs
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Qualitest
Dosage forms
FormRouteStrength
SuspensionOral
TabletOral
SuppositoryVaginal
CreamVaginal
TabletOral500 mg/1
TabletOral500.5 mg
Prices
Unit descriptionCostUnit
Silver Sulfadiazine 1% Cream 400 gm Jar36.48USD jar
Silver Sulfadiazine 1% Cream 50 gm Jar21.99USD jar
Silver Sulfadiazine 1% Cream 85 gm Jar19.99USD jar
Silver Sulfadiazine 1% Cream 25 gm Jar13.99USD jar
Sulfadiazine 500 mg tablet2.5USD tablet
Sulfazine EC 500 mg Enteric Coated Tabs0.42USD tab
Sulfazine ec 500 mg tablet0.38USD tablet
Sulfazine 500 mg tablet0.25USD tablet
Sulfadiazine powder0.13USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)255.5 dec °CPhysProp
water solubility77 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.09HANSCH,C ET AL. (1995)
logS-3.51ADME Research, USCD
pKa6.36SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.601 mg/mLALOGPS
logP0.25ALOGPS
logP0.39ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)6.99ChemAxon
pKa (Strongest Basic)2.01ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area97.97 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity64.2 m3·mol-1ChemAxon
Polarizability24.39 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9877
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6988
P-glycoprotein substrateNon-substrate0.9012
P-glycoprotein inhibitor INon-inhibitor0.913
P-glycoprotein inhibitor IINon-inhibitor0.9156
Renal organic cation transporterNon-inhibitor0.8437
CYP450 2C9 substrateNon-substrate0.8031
CYP450 2D6 substrateNon-substrate0.915
CYP450 3A4 substrateNon-substrate0.7671
CYP450 1A2 substrateNon-inhibitor0.9574
CYP450 2C9 inhibitorNon-inhibitor0.922
CYP450 2D6 inhibitorNon-inhibitor0.9548
CYP450 2C19 inhibitorNon-inhibitor0.9693
CYP450 3A4 inhibitorNon-inhibitor0.902
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8569
Ames testNon AMES toxic0.9206
CarcinogenicityNon-carcinogens0.9393
BiodegradationNot ready biodegradable0.9973
Rat acute toxicity1.8353 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9383
hERG inhibition (predictor II)Non-inhibitor0.8673
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.99 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0090000000-1bc83eabade65dc8953a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0910000000-bd163c77861c5a8afa49
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0900000000-260a572b5c7f3c070c26
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-052r-0900000000-580f983ba25c4cb3eb30
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-1900000000-8dc8c152ec6044f1c2e9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0090000000-23afa7ea3ef67a93a2e6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0pb9-3960000000-355dcad6c59ae9c75fb7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-4900000000-337c5e4fc08cc648b85d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4l-8900000000-63cd0dba3c4894d64ae1
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4l-9500000000-64c8a8332030e3f700a1
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05mo-9300000000-746250effd08ec8bf51b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0090000000-e8005ac37727f1c540d8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0pb9-2960000000-ff127258fb7c09ae3665
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-4900000000-4fa5b350b17254bc9a1a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4l-8900000000-4a998ad7772889643c1f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4l-9500000000-7e0d8190b4e7f7ced956
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05mo-9300000000-9cca42d677a6ef782a2c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-1900000000-4b5c2f7e29a6399f475c

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Aminobenzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / Aniline and substituted anilines / Pyrimidines and pyrimidine derivatives / Organosulfonamides / Heteroaromatic compounds / Aminosulfonyl compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
Aminobenzenesulfonamide / Benzenesulfonyl group / Aniline or substituted anilines / Pyrimidine / Organosulfonic acid amide / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Heteroaromatic compound / Aminosulfonyl compound / Sulfonyl
show 12 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
substituted aniline, sulfonamide, pyrimidines, sulfonamide antibiotic (CHEBI:9328)

Targets

Kind
Protein
Organism
Plasmodium falciparum
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dihydropteroate synthase activity
Specific Function
Not Available
Gene Name
Not Available
Uniprot ID
Q27738
Uniprot Name
Dihydropteroate synthetase
Molecular Weight
43370.845 Da
References
  1. de Araujo MV, Vieira EK, Silva Lazaro G, Conegero LS, Almeida LE, Barreto LS, da Costa NB Jr, Gimenez IF: Sulfadiazine/hydroxypropyl-beta-cyclodextrin host-guest system: Characterization, phase-solubility and molecular modeling. Bioorg Med Chem. 2008 May 15;16(10):5788-94. doi: 10.1016/j.bmc.2008.03.057. Epub 2008 Mar 27. [PubMed:18434167]
  2. Iliades P, Meshnick SR, Macreadie IG: Mutations in the Pneumocystis jirovecii DHPS gene confer cross-resistance to sulfa drugs. Antimicrob Agents Chemother. 2005 Feb;49(2):741-8. [PubMed:15673759]
  3. Prabhu V, Lui H, King J: Arabidopsis dihydropteroate synthase: general properties and inhibition by reaction product and sulfonamides. Phytochemistry. 1997 May;45(1):23-7. [PubMed:9127492]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data based on the findings of in vitro studies.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Komatsu K, Ito K, Nakajima Y, Kanamitsu Si, Imaoka S, Funae Y, Green CE, Tyson CA, Shimada N, Sugiyama Y: Prediction of in vivo drug-drug interactions between tolbutamide and various sulfonamides in humans based on in vitro experiments. Drug Metab Dispos. 2000 Apr;28(4):475-81. [PubMed:10725317]
  2. Clin-Info. (2006). In Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals (pp. L58). Canadian Pharmacists Association. [ISBN:1-894402-22-7]
  3. A Review on Drug Interactions in Oral Hypoglycemic Drugs by Mechanism of Cytochrome P450 Enzyme Inhibition [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:51