Identification
- Generic Name
- Acetyl sulfisoxazole
- DrugBank Accession Number
- DB14033
- Background
Sulfisoxazole acetyl is an ester of sulfisoxazole, a broad-spectrum sulfanilamide and a synthetic analog of para-aminobenzoic acid (PABA) with antibacterial activity. Sulfisoxazole acetyl competes with PABA for the bacterial enzyme, dihydropteroate synthase, preventing the incorporation of PABA into dihydrofolic acid, which is the precursor of folic acid. This process causes an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, resulting in cell growth arrest and cell death 2.
It is often combined with erythromycin to treat acute otitis media caused by the bacteria, haemophilus influenzae 3.
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Structure
Structure for Acetyl sulfisoxazole (DB14033)
- Weight
- Average: 309.34
Monoisotopic: 309.078327149 - Chemical Formula
- C13H15N3O4S
- Synonyms
- Sulfisoxazole acetyl
Pharmacology
- Indication
Acute, recurrent or chronic urinary tract infections (primarily pyelonephritis, pyelitis and cystitis) due to susceptible organisms (usually Escherichia coli, Klebsiella-Enterobacter, staphylococcus, Proteus mirabilis and, less frequently, Proteus vulgaris) in the absence of obstructive uropathy or foreign bodies 9
Meningococcal meningitis where the organism has been demonstrated to be susceptible. Haemophilus influenzae meningitis as adjunctive therapy with parenteral streptomycin 9
Meningococcal meningitis prophylaxis 9.
Acute otitis media due to Haemophilus influenzae when used concomitantly with adequate doses of penicillin or erythromycin (see appropriate labeling for prescribing information) 9.
Trachoma, inclusion conjunctivitis, nocardiosis, chancroid, toxoplasmosis as adjunctive therapy with pyrimethamine. Malaria due to chloroquine-resistant strains of Plasmodium falciparum, when used as adjunctive therapy 9.
Currently, the increasing frequency of resistant organisms is a limitation of the usefulness of antibacterial agents including the sulfonamides, especially in the treatment of chronic and recurrent urinary tract infections 9.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Chancroid •••••••••••• Used as adjunct in combination to treat Haemophilus influenzae meningitis •••••••••••• Treatment of Inclusion conjunctivitis •••••••••••• Adjunct therapy in treatment of Malaria •••••••••••• Treatment of Meningococcal meningitis •••••••••••• •••••••• •••••••••••• •• •• ••••••••••• - Contraindications & Blackbox Warnings
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Sulfisoxazole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with action against most gram-positive and many gram-negative organisms. Many strains of an individual species may be resistant to this drugf. Sulfonamides inhibit the 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. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus 6.
- Mechanism of action
Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid 6.
Target Actions Organism ADihydropteroate synthase inhibitorEscherichia coli (strain K12) - Absorption
Readily absorbed from the gastrointestinal tract 5.
In a pharmacokinetic study, the adjustments for variable renal clearances between oral and intravenous administration and using the unbound plasma concentrations, the bioavailability for an oral dose of sulfisoxazole was found to be 0.95 +/- 0.04 7.
- Volume of distribution
The sulfonamides are widely distributed throughout all body tissues 5.
It readily crosses the placental barrier and enters into fetal circulation and also crosses the blood-brain barrier. In healthy subjects, cerebrospinal fluid concentrations of sulfisoxazole vary; in patients with meningitis, however, concentrations of free drug in cerebrospinal fluid as high as 94 mcg/mL have been reported 9.
In a pharmacokinetic study, the apparent volume of distribution for total drug was 10.9 +/- 2.0 liters and 136 +/- 36 liters for the unbound drug, indicating that sulfisoxazole is primarily distributed extracellularly 7.
- Protein binding
Approximately 85% of a dose of sulfisoxazole is bound to plasma proteins, primarily to albumin; 65% to 72% of the unbound portion is in the nonacetylated form 9.
- Metabolism
Sulfisoxazole acetyl is a prodrug of sulfisoxazole. The acetyl group is added to make the drug poorly water-soluble and is hydrolyzed in vivo to the active drug 9, 11.
N1-acetyl sulfisoxazole is metabolized to sulfisoxazole by digestive enzymes in the gastrointestinal tract and is absorbed as sulfisoxazole. This enzymatic splitting is thought to be responsible for slower absorption and lower peak blood concentrations are achieved after administration of an equal oral dose of sulfisoxazole. With sustained administration of acetyl sulfisoxazole, blood concentrations approximate those of sulfisoxazole. Following a single 4 gram dose of acetyl sulfisoxazole to healthy volunteers, maximum plasma concentrations of sulfisoxazole ranged from 122 to 282 mcg/mL (mean, 181 mcg/mL) for the pediatric suspension and occurred between 2 and 6 hours postadministration of sulfisoxazole, in a pharmacokinetic study 9.
- Route of elimination
The mean urinary excretion recovery following oral administration of sulfisoxazole is 97% within 48 hours, of which 52% is the parent drug, and the remaining as the N4-acetylated metabolite. It is excreted in human milk 5.
Sulfisoxazole and its acetylated metabolites are excreted primarily by the kidneys through glomerular filtration 9.
- Half-life
The serum half-life is 10 -12 hours 5.
- Clearance
The clearance of sulfisoxazole is 18.7 +/- 3.9 ml/min for total drug and 232 +/- 64 ml/min for the unbound drug 7.
- Adverse Effects
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LD50=6800 mg/kg (Orally in mice) 10.
Sulfonamide-induced hypersensitivity reactions, although uncommon, can be severe. They can include rare life-threatening cutaneous reactions such as erythema multiform (Stevens-Johnson syndrome) and toxic epidermal necrolysis. Crystalluria may result in dysuria, renal colic, haematuria and acute renal obstruction 8.
Other infrequent reactions include granulocytopenia, agranulocytosis, aplastic anemia, thrombocytopenic purpura and toxic hepatitis. Rarely, hemolysis may occur in individuals deficient in glucose-6-phosphate dehydrogenase 8.
The severe or irreversible adverse effects of sulfisoxazole, which give rise to more complications which may include: nephrotoxicity, blood dyscrasias, interstitial nephritis, hematuria, crystalluria, oliguria, anuria, lumbar pain, and tubular necrosis 8.
The symptomatic adverse reactions produced by sulfisoxazole are more or less tolerable and if severe, may be treated symptomatically, these include anorexia, diarrhea, rashes, pruritus, nausea and vomiting, hypersensitivity reactions, Photosensitivity reactions 5.
Overdosage: Continuously forced diuresis may be beneficial and an alkaline urine should be initiated 5.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbrocitinib The metabolism of Abrocitinib can be decreased when combined with Acetyl sulfisoxazole. Acarbose The therapeutic efficacy of Acarbose can be increased when used in combination with Acetyl sulfisoxazole. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Acetyl sulfisoxazole. Acetohexamide The therapeutic efficacy of Acetohexamide can be increased when used in combination with Acetyl sulfisoxazole. Acetylsalicylic acid The metabolism of Acetylsalicylic acid can be decreased when combined with Acetyl sulfisoxazole. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Sulfisoxazole unknown 740T4C525W 127-69-5 NHUHCSRWZMLRLA-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Gantrisin Suspension 0.5 g/5mL Oral Genentech, Inc. 1953-12-04 2011-07-08 US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl Acetyl sulfisoxazole (600 mg/5mL) + Erythromycin ethylsuccinate (200 mg/5mL) Granule, for suspension Oral Physicians Total Care, Inc. 2000-10-11 Not applicable US Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl Acetyl sulfisoxazole (600 mg/5mL) + Erythromycin ethylsuccinate (200 mg/5mL) Granule, for suspension Oral Physicians Total Care, Inc. 1995-02-01 2011-04-30 US Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl Acetyl sulfisoxazole (600 mg/5mL) + Erythromycin ethylsuccinate (200 mg/5mL) Granule, for suspension Oral Rebel Distributors 1988-05-20 Not applicable US Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl Acetyl sulfisoxazole (600 mg/5mL) + Erythromycin ethylsuccinate (200 mg/5mL) Granule, for suspension Oral Teva Women's Health 1998-06-01 2014-11-30 US Pediazole Acetyl sulfisoxazole (600 mg / 5 mL) + Erythromycin ethylsuccinate (200 mg / 5 mL) Powder, for suspension Oral Amdipharm Limited 1983-12-31 2017-07-17 Canada 
Categories
- ATC Codes
- G01AE10 — Combinations of sulfonamides
- Drug Categories
- Amides
- Amines
- Aniline Compounds
- Anti-Bacterial Agents
- Benzene Derivatives
- Benzenesulfonamides
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 Enzyme Inhibitors
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Sulfanilamides
- Sulfonamide Antibacterial
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- 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 / Organosulfonic acids and derivatives / Isoxazoles / Heteroaromatic compounds / Aminosulfonyl compounds / Acetamides / Amino acids and derivatives / Oxacyclic compounds / Azacyclic compounds show 5 more
- Substituents
- Acetamide / Amine / Amino acid or derivatives / Aminobenzenesulfonamide / Aminosulfonyl compound / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Azacycle / Azole / Benzenesulfonyl group show 18 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- WBT5QH3KED
- CAS number
- 80-74-0
- InChI Key
- JFNWFXVFBDDWCX-UHFFFAOYSA-N
- InChI
- InChI=1S/C13H15N3O4S/c1-8-9(2)15-20-13(8)16(10(3)17)21(18,19)12-6-4-11(14)5-7-12/h4-7H,14H2,1-3H3
- IUPAC Name
- N-(4-aminobenzenesulfonyl)-N-(3,4-dimethyl-1,2-oxazol-5-yl)acetamide
- SMILES
- CC(=O)N(C1=C(C)C(C)=NO1)S(=O)(=O)C1=CC=C(N)C=C1
References
- General References
- Suber RL, Lee C, Torosian G, Edds GT: Pharmacokinetics of sulfisoxazole compared in humans and two monogastric animal species. J Pharm Sci. 1981 Sep;70(9):981-4. [Article]
- Acetyl Sulfisoxazole [Link]
- ERYTHROMYCIN ETHYLSUCCINATE AND SULFISOXAZOLE ACETYL [Link]
- Sulfisoxazole [Link]
- Sulfadiazine or Sulfisoxazole [Link]
- Sulfisoxazole [Link]
- Comparison of the disposition of total and unbound sulfisoxazole after single and multiple dosing [Link]
- Gantrisin [Link]
- Gantrisin Description [Link]
- Sulfisoxazole, ToxNET [Link]
- Sulfisoxazole [Link]
- External Links
- PubChem Compound
- 6662
- ChemSpider
- 6410
- ChEBI
- 135975
- ChEMBL
- CHEMBL1200910
- ZINC
- ZINC000000002114
- MSDS
- Download (200 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Granule, for suspension Oral Suspension Oral 0.5 g/5mL Powder, for suspension Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 192 - 195 MSDS - Predicted Properties
Property Value Source Water Solubility 0.136 mg/mL ALOGPS logP 1.02 ALOGPS logP 0.72 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 18.1 Chemaxon pKa (Strongest Basic) 1.61 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 106.5 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 77.48 m3·mol-1 Chemaxon Polarizability 30.24 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0109000000-0fd99f2b71082d7cf3ca Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0039000000-8f388b9076ee4139e34f Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-08fr-2935000000-f1d758420844846473d4 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4i-0395000000-a36cfdc8502bb70f28d2 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-9110000000-f9bb8a321140a0b6ecfe Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a6r-1900000000-4da5cac142d1b47057a2 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 178.3536715 predictedDarkChem Lite v0.1.0 [M-H]- 170.93579 predictedDeepCCS 1.0 (2019) [M+H]+ 179.5472715 predictedDarkChem Lite v0.1.0 [M+H]+ 173.29381 predictedDeepCCS 1.0 (2019) [M+Na]+ 179.0253715 predictedDarkChem Lite v0.1.0 [M+Na]+ 180.1588 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Metal ion binding
- Specific Function
- Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives.
- Gene Name
- folP
- Uniprot ID
- P0AC13
- Uniprot Name
- Dihydropteroate synthase
- Molecular Weight
- 30614.855 Da
References
- 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. [Article]
- Jorgensen JH, Crawford SA, Fiebelkorn KR: Susceptibility of Neisseria meningitidis to 16 antimicrobial agents and characterization of resistance mechanisms affecting some agents. J Clin Microbiol. 2005 Jul;43(7):3162-71. [Article]
- Fiebelkorn KR, Crawford SA, Jorgensen JH: Mutations in folP associated with elevated sulfonamide MICs for Neisseria meningitidis clinical isolates from five continents. Antimicrob Agents Chemother. 2005 Feb;49(2):536-40. [Article]
- 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. [Article]
- Sulfisoxazole [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- 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. [Article]
Drug created at May 17, 2018 17:14 / Updated at January 08, 2021 01:07