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Identification
Name Sulfamethoxazole
Accession Number DB01015 (APRD00076)
Type small molecule
Groups approved
Description

A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p208)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Apo-Sulfamethoxazole
Azo-Gantanol
Bactrimel
Gamazole
Gantanol
Gantanol-DS
Metoxal
Radonil
Septran
Simsinomin
Sinomin
Sulfamethalazole
Sulfamethoxazol
Sulfamethoxizole
Sulfamethylisoxazole
Sulfisomezole
Sulpha-Methoxizole
Sulphamethalazole
Sulphamethoxazol
Sulphamethoxazole
Sulphamethoxazole BP 98
Sulphamethylisoxazole
Sulphisomezole
Trib
Urobak
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Brand mixtures
Brand Name Ingredients
Apo Sulfatrim DS Tab Sulfamethoxazole + Trimethoprim
Apo Sulfatrim Pediatric Sulfamethoxazole + Trimethoprim
Apo Sulfatrim Tab Sulfamethoxazole + Trimethoprim
Bactrim DS Roche Tab Sulfamethoxazole + Trimethoprim
Bactrim Roche Inj Sulfamethoxazole + Trimethoprim
Bactrim Roche Suspension Paediatric Sulfamethoxazole + Trimethoprim
Bactrim Roche Tab Sulfamethoxazole + Trimethoprim
Novo-Trimel DS Tab Sulfamethoxazole + Trimethoprim
Novo-Trimel Oral Sus Sulfamethoxazole + Trimethoprim
Novo-Trimel Tab Sulfamethoxazole + Trimethoprim
Protrin DF Tab Sulfamethoxazole + Trimethoprim
Protrin Tab Sulfamethoxazole + Trimethoprim
Riva-Sep DS Sulfamethoxazole + Trimethoprim
Roubac Tab 160/800 Sulfamethoxazole + Trimethoprim
Roubac Tab 80/400 Sulfamethoxazole + Trimethoprim
Septra Sulfamethoxazole + Trimethoprim
Septra DS Tablets Sulfamethoxazole + Trimethoprim
Septra Injection Sulfamethoxazole + Trimethoprim
Septra Pediatric Suspension Sulfamethoxazole + Trimethoprim
Sulfamethoxazole and Trimethoprim Tablets Sulfamethoxazole + Trimethoprim
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Categories
  • Anti-Infective Agents
  • Anti-Infectives
  • Sulfonamides
CAS number 723-46-6
Weight Average: 253.278
Monoisotopic: 253.052111923
Chemical Formula C10H11N3O3S
InChI Key InChIKey=JLKIGFTWXXRPMT-UHFFFAOYSA-N
InChI
InChI=1S/C10H11N3O3S/c1-7-6-10(12-16-7)13-17(14,15)9-4-2-8(11)3-5-9/h2-6H,11H2,1H3,(H,12,13)
Plain Text
IUPAC Name
4-amino-N-(5-methyl-1,2-oxazol-3-yl)benzene-1-sulfonamide
SMILES
CC1=CC(NS(=O)(=O)C2=CC=C(N)C=C2)=NO1
Plain Text
Mass Spec show (9.61 KB)
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
  • Sulfanilamides
Substructures
  • Sulfonyls
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Isoxazoles
  • Benzenesulfonamides
  • Heterocyclic compounds
  • Aromatic compounds
  • Oxazoles
  • Sulfanilamides
  • Sulfonamides
  • Anilines
Pharmacology
Indication For the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections.
Pharmacodynamics Sulfamethoxazole is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethoxazole is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA. Sulfamethoxazole is normally given in combination with Trimethoprim, a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid. Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either Trimethoprim or Sulfamethoxazole alone.
Mechanism of action Sulfonamides inhibit the enzymatic conversion of pteridine and p-aminobenzoic acid (PABA) to dihydropteroic acid by competing with PABA for binding to dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth. Pyrimethamine and trimethoprim inhibit dihydrofolate reductase, another step in THF synthesis, and therefore act synergistically with the sulfonamides.
Absorption Rapidly absorbed following oral administration. Also well-absorbed topically.
Volume of distribution Not Available
Protein binding 70%
Metabolism Hepatic. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation, although the glucuronide conjugate has been identified.
Route of elimination Not Available
Half life 10 hours
Clearance Not Available
Toxicity Sulfamethoxazole may cause nausea, vomiting, diarrhea and hypersensitivity reactions. Hematologic effects such as anemia, agranulocytosis, thrombocytopenia and hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency may also occur. Sulfamethoxazole may displace bilirubin from albumin binding sites causing jaundice or kernicterus in newborns.
Affected organisms
  • Gram negative and gram positive bacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
  • Ascot hosp pharmaceuticals inc div travenol laboratories inc
  • Barr laboratories inc
  • Heather drug co inc
  • Sandoz inc
  • Watson laboratories inc
  • Shionogi usa inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Sulfamethoxazole-TMP DS 800-160 mg tablet 0.94 USD tablet
Sulfamethoxazole powder 0.41 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 167 °C PhysProp
water solubility 610 mg/L (at 37 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 0.89 HANSCH,C ET AL. (1995)
logS -2.62 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 4.59e-01 g/l ALOGPS
logP 0.79 ALOGPS
logP 0.79 ChemAxon
logS -2.7 ALOGPS
pKa (strongest acidic) 6.16 ChemAxon
pKa (strongest basic) 1.97 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 98.22 ChemAxon
rotatable bond count 2 ChemAxon
refractivity 64.5 ChemAxon
polarizability 24.99 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00447 Link_out
KEGG Compound C07315 Link_out
PubChem Compound 5329 Link_out
PubChem Substance 46508111 Link_out
ChemSpider 5138 Link_out
ChEBI 9332 Link_out
ChEMBL 9332 Link_out
Therapeutic Targets Database DNC001393 Link_out
PharmGKB PA451544 Link_out
Drug Product Database 421480 Link_out
RxList http://www.rxlist.com/cgi/generic3/gantanol.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Sulfamethoxazole Link_out
ATC Codes
  • J01EC01
AHFS Codes
  • 08:12.20
PDB Entries
FDA label Not Available
MSDS show (35 KB)
Interactions
Drug Interactions
Drug Interaction
Chlorpropamide Sulfonamide/sulfonylurea: possible hypoglycemia
Cyclosporine The sulfonamide decreases the effect of cyclosporine
Methotrexate The sulfamide increases the toxicity of methotrexate
Pralatrexate Decreases renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects.
Tobramycin Increased risk of nephrotoxicity
Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Sulfamethoxazole. Consider alternate therapy or monitor for changes in Sulfamethoxazole therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed.
Warfarin Sulfamethoxazole may increase the anticoagulant effect of warfarin by decreasing its metabolism. Consider alternate therapy or monitor for changes in prothrombin time if sulfamethoxazole is initiated, discontinued or dose changed.
Food Interactions
  • Do not take calcium, aluminium, magnesium or iron supplements within 2 hours of taking this medication.
  • Take on empty stomach: 1 hour before or 2 hours after meals.
  • Take with a full glass of water.
Targets

1. Dihydropteroate synthase

Pharmacological action: yes
Actions: inhibitor

DHPS catalyzes the formation of the immediate precursor of folic acid. It is implicated in resistance to sulfonamide

Organism class: bacterial
UniProt ID: P0AC13 Link_out
Gene: folP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hong YL, Hossler PA, Calhoun DH, Meshnick SR: Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63. Pubmed

2. FolC bifunctional protein [Includes: Folylpolyglutamate synthase

Pharmacological action: yes
Actions: inhibitor

Conversion of folates to polyglutamate derivatives

Organism class: bacterial
UniProt ID: P08192 Link_out
Gene: folC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Winstanley PA, Mberu EK, Szwandt IS, Breckenridge AM, Watkins WM: In vitro activities of novel antifolate drug combinations against Plasmodium falciparum and human granulocyte CFUs. Antimicrob Agents Chemother. 1995 Apr;39(4):948-52. Pubmed
Enzymes

1. Arylamine N-acetyltransferase 1

Actions: substrate

Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens

UniProt ID: P18440 Link_out
Gene: NAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

2. Arylamine N-acetyltransferase 2

Actions: substrate

Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens

UniProt ID: P11245 Link_out
Gene: NAT2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

3. Cytochrome P450 2C9

Actions: substrate, inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Cribb AE, Spielberg SP, Griffin GP: N4-hydroxylation of sulfamethoxazole by cytochrome P450 of the cytochrome P4502C subfamily and reduction of sulfamethoxazole hydroxylamine in human and rat hepatic microsomes. Drug Metab Dispos. 1995 Mar;23(3):406-14. Pubmed
  4. 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. Epub 2009 Nov 24. Pubmed

4. Prostaglandin G/H synthase 1

Actions: substrate

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

5. UDP-glucuronosyltransferase 1-9

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols

UniProt ID: O60656 Link_out
Gene: UGT1A9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

6. Cytochrome P450 2C8

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Carriers

1. Serum albumin

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed
  2. Angelakou A, Valsami G, Koupparis M, Macheras P: Use of 1-anilino-8-napthalenesulphonate as an ion probe for the potentiometric study of the binding of sulphonamides to bovine serum albumin and plasma. J Pharm Pharmacol. 1993 May;45(5):434-8. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19