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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
Gantanol (tn)Not AvailableNot Available
SMXNot AvailableNot Available
SulfamethoxazoleNot 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 KeyJLKIGFTWXXRPMT-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
Not Available
Sulfamethoxazole N1-glucuronideDetails
Sulfamethoxazole
Sulfamethoxazole N4-hydroxylamineDetails
5-Hydroxysulfamethoxazole
N4-Acetyl-5-OH-sulfamethoxazoleDetails
N4-Acetylsulfamethoxazole
Not Available
N4-Acetyl-5-OH-sulfamethoxazoleDetails
Sulfamethoxazole N4-hydroxylamine
Not Available
Nitroso-sulfamethoxazoleDetails
Nitroso-sulfamethoxazole
Not Available
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.

Targets

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

Enzymes

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

Carriers

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

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Drug created on June 13, 2005 07:24 / Updated on January 14, 2014 20:32