Details of the Drug

General Information of Drug (ID: DMXLT8C)

• Drug Name: Sulfisoxazole
• Synonyms: Accuzole; Alphazole; Amidoxal; Astrazolo; Azosulfizin; Bactesulf; Barazae; Chemouag; Cosoxazole; Dorsulfan; ERYZOLE; Entusil; Entusul; Ganda; Gantrisin; Gantrisine; Gantrisona; Gantrosan; Isoxamin; Neazolin; Neoxazoi; Neoxazol; Novazolo; Novosaxazole; Pancid; Renosulfan; Resoxol; Roxosul; Roxoxol; SOXO; Saxosozine; Sodizole; Solfafurazolo; Sosol; Soxamide; Soxazole; Soxisol; Soxitabs; Soxomide; Stansin; Sulbio; Sulfadimethylisoxazole; Sulfafurazol; Sulfafurazole; Sulfafurazolum; Sulfagan; Sulfagen; Sulfaisoxazole; Sulfalar; Sulfapolar; Sulfasol; Sulfasoxazole; Sulfasoxizole; Sulfazin; Sulfisin; Sulfisonazole; Sulfisoxasole; Sulfisoxazol; Sulfisoxazolum; Sulfizin; Sulfizol; Sulfizole; Sulfofurazole; Sulfoxol; Suloxsol; Sulphadimethylisoxazole; Sulphafuraz; Sulphafurazol; Sulphafurazole; Sulphafurazolum; Sulphaisoxazole; Sulphisoxazol; Sulphisoxazole; Sulphofurazole; Sulsoxin; Thiasin; Unisulf; Urisoxin; Uritrisin; Urogan; Vagilia; Azo Gantrisin; Component of Azo Gantrisin; Component of Azo Gantrisin Accuzole; Dorsulfan warthausen; Roxosul tablets; Solfafurazolo [DCIT]; Sulfafuraz ole; Sulfisoxazole [USAN]; Sulfisoxazole dialamine; NU 445; Component of Azo-Sulfizin; G-sox; Gantrisin (TN); J-Sul; Koro-sulf; Norilgan-S; SK-Soxazole; Sulfafurazole (INN); Sulfafurazolum [INN-Latin]; Sulfazin (VAN); Sulfisoxazole-Carc; Tl-azole; US-67; V-Sul; Sulfisoxazole (JP15/USP); U.S.-67; 3,4-Dimethyl-5-sulfanilamidoisoxazole; 3,4-Dimethyl-5-sulfonamidoisoxazole; 3,4-Dimethyl-5-sulphanilamidoisoxazole; 3,4-Dimethyl-5-sulphonamidoisoxazole; 3,4-Dimethylisoxale-5-sulfanilamide; 3,4-Dimethylisoxazole-5-sulfanilamide; 3,4-Dimethylisoxazole-5-sulphanilamide; 3,4-dimethylisoaxazole-5-sulfanilimide; 5-Sulfanilamido-3,4-dimethyl-isoxazole; 5-Sulfanilamido-3,4-dimethylisoxazole; 5-Sulphanilamido-3,4-dimethyl-isoxazole

Indication

Disease Entry	ICD 11	Status	REF
Acute otitis media	AB00	Approved	[1]
Chancroid	N.A.	Approved	[1]
Inclusion conjunctivitis	N.A.	Approved	[1]
Meningococcal meningitis	N.A.	Approved	[1]
Plasmodium falciparum malaria	1F40	Approved	[1]
Trachoma	N.A.	Approved	[1]
Urinary tract infection	GC08	Approved	[2]

• Therapeutic Class: Antiinfective Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 267.31
  Logarithm of the Partition Coefficient (xlogp); 1
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
  Bioavailability: 96% of drug becomes completely available to its intended biological destination(s) [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.3 mL/min/kg [5]
  Elimination: 49% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 7.4 hours [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 249.52437 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.079% [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.17 L/kg [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.13 mg/mL [3]
• Chemical Identifiers:
  Formula: C11H13N3O3S
  IUPAC Name: 4-amino-N-(3,4-dimethyl-1,2-oxazol-5-yl)benzenesulfonamide
  Canonical SMILES: CC1=C(ON=C1C)NS(=O)(=O)C2=CC=C(C=C2)N
  InChI: InChI=1S/C11H13N3O3S/c1-7-8(2)13-17-11(7)14-18(15,16)10-5-3-9(12)4-6-10/h3-6,14H,12H2,1-2H3
  InChIKey: NHUHCSRWZMLRLA-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5344
  ChEBI ID: CHEBI:102484
  CAS Number: 127-69-5
  DrugBank ID: DB00263
  TTD ID: D09TBD
  INTEDE ID: DR1510
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Dihydropteroate synthetase (Bact folP)	TT4ILYC	DHPS_ECOLI	Inhibitor	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Gene/Protein Processing	[9]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Gene/Protein Processing	[10]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Sulfisoxazole (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[11]
Repaglinide	DM5SXUV	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Repaglinide.	Acute diabete complication [5A2Y]	[12]
Glibenclamide	DM8JXPZ	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Glibenclamide.	Acute diabete complication [5A2Y]	[12]
Tolazamide	DMIHRNA	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Tolazamide.	Acute diabete complication [5A2Y]	[13]
Nateglinide	DMLK2QH	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Nateglinide.	Acute diabete complication [5A2Y]	[12]
Insulin-glulisine	DMQI0FU	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Insulin-glulisine.	Acute diabete complication [5A2Y]	[12]
Acetohexamide	DMR6N7H	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Acetohexamide.	Acute diabete complication [5A2Y]	[13]
Insulin-aspart	DMX7V28	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Insulin-aspart.	Acute diabete complication [5A2Y]	[14]
Glipizide	DMZA5PQ	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Glipizide.	Acute diabete complication [5A2Y]	[12]
Thioguanine	DM7NKEV	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Thioguanine.	Acute myeloid leukaemia [2A60]	[15]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[16]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[17]
Mycophenolic acid	DMRBMAU	Moderate	Altered absorption of Sulfisoxazole due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[18]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Cannabidiol.	Epileptic encephalopathy [8A62]	[19]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[20]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[21]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[22]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[23]
Methotrexate	DM2TEOL	Moderate	Increased plasma concentration of Sulfisoxazole and Methotrexate due to competitive binding of plasma proteins.	Leukaemia [2A60-2B33]	[24]
Porfimer Sodium	DM7ZWNY	Moderate	Increased risk of photosensitivity reactions by the combination of Sulfisoxazole and Porfimer Sodium.	Lung cancer [2C25]	[25]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[26]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Idelalisib.	Mature B-cell leukaemia [2A82]	[27]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Clofarabine.	Mature B-cell lymphoma [2A85]	[28]
Methoxsalen	DME8FZ9	Moderate	Increased risk of photosensitivity reactions by the combination of Sulfisoxazole and Methoxsalen.	Mycosis fungoides [2B01]	[11]
Prilocaine	DMI7DZ2	Major	Increased risk of methemoglobinemia by the combination of Sulfisoxazole and Prilocaine.	Pain [MG30-MG3Z]	[29]
Verteporfin	DMIY6DB	Moderate	Increased risk of photosensitivity reactions by the combination of Sulfisoxazole and Verteporfin.	Psoriasis [EA90]	[19]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[19]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Sulfisoxazole and Naltrexone.	Substance abuse [6C40]	[30]
Warfarin	DMJYCVW	Major	Decreased metabolism of Sulfisoxazole caused by Warfarin mediated inhibition of CYP450 enzyme.	Supraventricular tachyarrhythmia [BC81]	[31]
Tolbutamide	DM02AWV	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Tolbutamide.	Type 2 diabetes mellitus [5A11]	[13]
Chlorpropamide	DMPHZQE	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Chlorpropamide.	Type 2 diabetes mellitus [5A11]	[13]
Insulin-detemir	DMOA4VW	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Insulin-detemir.	Type-1/2 diabete [5A10-5A11]	[12]
Insulin degludec	DMPL395	Moderate	Increased risk of hypoglycemia by the combination of Sulfisoxazole and Insulin degludec.	Type-1/2 diabete [5A10-5A11]	[12]

References

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• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] BDDCS applied to over 900 drugs
• [4] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [7] Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63.
• [8] 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.
• [9] A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97.
• [10] Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1. J Biochem Mol Toxicol. 2017 Oct;31(10).
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• [13] Christensen LK, Hansen JM, Kristensen M "Sulphaphenazole-induced hypoglycemic attacks in tolbutamide-treated diabetics." Lancet 2 (1963): 1298-301. [PMID: 14071924]
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• [17] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [18] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
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• [20] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
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• [23] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
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• [26] Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
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• [28] Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
• [29] Canadian Pharmacists Association.
• [30] Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.
• [31] Cook DE, Ponte CD "Suspected trimethoprim sulfamethoxazole induced hypoprothrombinemia." J Fam Pract 39 (1994): 589-91. [PMID: 7798864]