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Identification
NameSulfamethoxazole
Accession NumberDB01015  (APRD00076)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
3-(p-Aminophenylsulfonamido)-5-methylisoxazoleNot AvailableNot Available
3-Sulfanilamido-5-methylisoxazoleNot AvailableNot Available
4-Amino-N-(5-methyl-3-isoxazolyl)benzenesulfonamideNot AvailableNot Available
SMXNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
GantanolNot Available
SinominNot Available
UrobakNot Available
Brand mixtures
Brand NameIngredients
Apo-SulfatrimSulfamethoxazole + Trimethoprim
Apo-Sulfatrim DSSulfamethoxazole + Trimethoprim
Apo-Sulfatrim PediatricSulfamethoxazole + Trimethoprim
BactrimSulfamethoxazole + Trimethoprim
BactrimelSulfamethoxazole + Trimethoprim
Novo-TrimelSulfamethoxazole + Trimethoprim
Novo-Trimel DSSulfamethoxazole + Trimethoprim
ProtrinSulfamethoxazole + Trimethoprim
Protrin DFSulfamethoxazole + Trimethoprim
Riva-Sep DSSulfamethoxazole + Trimethoprim
RoubacSulfamethoxazole + Trimethoprim
SeptraSulfamethoxazole + Trimethoprim
Septra DSSulfamethoxazole + Trimethoprim
Septra InjectionSulfamethoxazole + Trimethoprim
Septra Pediatric SuspensionSulfamethoxazole + Trimethoprim
SeptranSulfamethoxazole + Trimethoprim
Categories
CAS number723-46-6
WeightAverage: 253.278
Monoisotopic: 253.052111923
Chemical FormulaC10H11N3O3S
InChI KeyInChIKey=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)
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
Mass Specshow(9.61 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentAminobenzenesulfonamides
Alternative parentsSulfonylanilines; Primary Aromatic Amines; Isoxazoles; Sulfonyls; Sulfonamides; Polyamines
Substituentsaniline; primary aromatic amine; sulfonyl; sulfonic acid derivative; azole; sulfonamide; isoxazole; polyamine; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Pharmacology
IndicationFor the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections.
PharmacodynamicsSulfamethoxazole 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 actionSulfonamides 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.
AbsorptionRapidly absorbed following oral administration. Also well-absorbed topically.
Volume of distributionNot Available
Protein binding70%
Metabolism

Hepatic. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation, although the glucuronide conjugate has been identified.

SubstrateEnzymesProduct
Sulfamethoxazole
5-HydroxysulfamethoxazoleDetails
Sulfamethoxazole
N4-AcetylsulfamethoxazoleDetails
Sulfamethoxazole
    Sulfamethoxazole N1-glucuronideDetails
    Sulfamethoxazole
    Sulfamethoxazole N4-hydroxylamineDetails
    5-Hydroxysulfamethoxazole
    N4-Acetyl-5-OH-sulfamethoxazoleDetails
    N4-Acetylsulfamethoxazole
      N4-Acetyl-5-OH-sulfamethoxazoleDetails
      Sulfamethoxazole N4-hydroxylamine
        Nitroso-sulfamethoxazoleDetails
        Nitroso-sulfamethoxazole
          Sulfamethoxazole GSH conjugateDetails
          Route of eliminationNot Available
          Half life10 hours
          ClearanceNot Available
          ToxicitySulfamethoxazole 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
          PathwaysNot Available
          SNP Mediated EffectsNot Available
          SNP Mediated Adverse Drug ReactionsNot Available
          ADMET
          Predicted ADMET features
          Property Value Probability
          Human Intestinal Absorption + 1.0
          Blood Brain Barrier + 0.9382
          Caco-2 permeable - 0.5346
          P-glycoprotein substrate Non-substrate 0.8884
          P-glycoprotein inhibitor I Non-inhibitor 0.9362
          P-glycoprotein inhibitor II Non-inhibitor 0.8754
          Renal organic cation transporter Non-inhibitor 0.9195
          CYP450 2C9 substrate Non-substrate 0.7652
          CYP450 2D6 substrate Non-substrate 0.9115
          CYP450 3A4 substrate Non-substrate 0.7632
          CYP450 1A2 substrate Non-inhibitor 0.9045
          CYP450 2C9 substrate Non-inhibitor 0.9071
          CYP450 2D6 substrate Non-inhibitor 0.9231
          CYP450 2C19 substrate Non-inhibitor 0.9025
          CYP450 3A4 substrate Non-inhibitor 0.9744
          CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7151
          Ames test Non AMES toxic 0.9132
          Carcinogenicity Non-carcinogens 0.8193
          Biodegradation Not ready biodegradable 0.9882
          Rat acute toxicity 1.6422 LD50, mol/kg Not applicable
          hERG inhibition (predictor I) Weak inhibitor 0.9143
          hERG inhibition (predictor II) Non-inhibitor 0.8956
          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
          FormRouteStrength
          TabletOral
          Prices
          Unit descriptionCostUnit
          Sulfamethoxazole-TMP DS 800-160 mg tablet0.94USDtablet
          Sulfamethoxazole powder0.41USDg
          DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
          PatentsNot Available
          Properties
          Statesolid
          Experimental Properties
          PropertyValueSource
          melting point167 °CPhysProp
          water solubility610 mg/L (at 37 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
          logP0.89HANSCH,C ET AL. (1995)
          logS-2.62ADME Research, USCD
          Predicted Properties
          PropertyValueSource
          water solubility4.59e-01 g/lALOGPS
          logP0.79ALOGPS
          logP0.79ChemAxon
          logS-2.7ALOGPS
          pKa (strongest acidic)6.16ChemAxon
          pKa (strongest basic)1.97ChemAxon
          physiological charge-1ChemAxon
          hydrogen acceptor count4ChemAxon
          hydrogen donor count2ChemAxon
          polar surface area98.22ChemAxon
          rotatable bond count2ChemAxon
          refractivity64.5ChemAxon
          polarizability24.99ChemAxon
          number of rings2ChemAxon
          bioavailability1ChemAxon
          rule of fiveYesChemAxon
          Ghose filterYesChemAxon
          Veber's ruleNoChemAxon
          MDDR-like ruleNoChemAxon
          Spectra
          SpectraNot Available
          References
          Synthesis Reference

          Yasushi Takagishi, Kiichiro Ohsuga, Sadao Ohama, “Suppository containing sulfamethoxazole/trimethoprim complex and process for preparing the same.” U.S. Patent US4461765, issued December, 1975.

          US4461765
          General ReferenceNot Available
          External Links
          ResourceLink
          KEGG DrugD00447
          KEGG CompoundC07315
          PubChem Compound5329
          PubChem Substance46508111
          ChemSpider5138
          ChEBI9332
          ChEMBLCHEMBL443
          Therapeutic Targets DatabaseDNC001393
          PharmGKBPA451544
          Drug Product Database421480
          RxListhttp://www.rxlist.com/cgi/generic3/gantanol.htm
          WikipediaSulfamethoxazole
          ATC CodesJ01EC01
          AHFS Codes
          • 08:12.20
          PDB Entries
          FDA labelNot Available
          MSDSshow(35 KB)
          Interactions
          Drug Interactions
          Drug
          ChlorpropamideSulfonamide/sulfonylurea: possible hypoglycemia
          CyclosporineThe sulfonamide decreases the effect of cyclosporine
          MethotrexateThe sulfamide increases the toxicity of methotrexate
          PralatrexateDecreases renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects.
          TobramycinIncreased risk of nephrotoxicity
          TolbutamideTolbutamide, 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.
          WarfarinSulfamethoxazole 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.

          1. Dihydropteroate synthase

          Kind: protein

          Organism: Escherichia coli (strain K12)

          Pharmacological action: yes

          Actions: inhibitor

          Components

          Name UniProt ID Details
          Dihydropteroate synthase P0AC13 Details

          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. Bifunctional protein FolC

          Kind: protein

          Organism: Escherichia coli (strain K12)

          Pharmacological action: yes

          Actions: inhibitor

          Components

          Name UniProt ID Details
          Bifunctional protein FolC P08192 Details

          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

          1. Arylamine N-acetyltransferase 1

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Arylamine N-acetyltransferase 1 P18440 Details

          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

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Arylamine N-acetyltransferase 2 P11245 Details

          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

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate inhibitor

          Components

          Name UniProt ID Details
          Cytochrome P450 2C9 P11712 Details

          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

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          Prostaglandin G/H synthase 1 P23219 Details

          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

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate

          Components

          Name UniProt ID Details
          UDP-glucuronosyltransferase 1-9 O60656 Details

          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

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: inhibitor

          Components

          Name UniProt ID Details
          Cytochrome P450 2C8 P10632 Details

          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

          Kind: protein

          Organism: Human

          Pharmacological action: unknown

          Actions: substrate inhibitor

          Components

          Name UniProt ID Details
          Cytochrome P450 3A4 P08684 Details

          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

          1. Serum albumin

          Kind: protein

          Organism: Human

          Pharmacological action: no

          Components

          Name UniProt ID Details
          Serum albumin P02768 Details

          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 January 14, 2014 20:32