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Identification
NameBalsalazide
Accession NumberDB01014  (APRD00141)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Balsalazide is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease. It is sold under the name “Colazal” in the US and “Colazide” in the UK.

The chemical name is (E)-5-[[-4-(2-carboxyethyl) aminocarbonyl] phenyl]azo] -2-hydroxybenzoic acid. It is usually administered as the disodium salt.

Balsalazide releases mesalazine, also known as 5-aminosalicylic acid, or 5-ASA, in the large intestine. Its advantage over that drug in the treatment of Ulcerative colitis is believed to be the delivery of the active agent past the small intestine to the large intestine, the active site of ulcerative colitis.

Structure
Thumb
Synonyms
(e)-5-((4-(((2-Carboxyethyl)amino)carbonyl)phenyl)azo)-2-hydroxybenzoic acid
(e)-5-({p-[(2-carboxyethyl)carbamoyl]phenyl}azo)-2-salicylic acid
3-(2-{4-[(2-carboxyethyl)carbamoyl]phenyl}hydrazinylidene)-6-oxocyclohexa-1,4-diene-1-carboxylic acid
5-[4-(2-Carboxy-ethylcarbamoyl)-phenylazo]-2-hydroxy-benzoic acid
Balsalazida
Balsalazido
Balsalazidum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Balsalazide Disodiumcapsule750 mg/1oralOceanside Pharmaceuticals2000-07-18Not applicableUs
Colazalcapsule750 mg/1oralCardinal Health2000-07-18Not applicableUs
Colazalcapsule750 mg/1oralSalix Pharmaceuticals, Inc.2000-07-18Not applicableUs
Giazotablet, film coated1.1 g/1oralSalix Pharmaceuticals, Inc.2012-02-02Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Balsalazide Disodiumcapsule750 mg/1oralRoxane Laboratories, Inc2007-12-28Not applicableUs
Balsalazide Disodiumtablet1.1 g/1oralPar Pharmaceutical Inc.2015-07-01Not applicableUs
Balsalazide Disodiumcapsule750 mg/1oralAmerican Health Packaging2014-07-31Not applicableUs
Balsalazide Disodiumcapsule750 mg/1oralApotex Corp.2007-12-28Not applicableUs
Balsalazide Disodiumcapsule750 mg/1oralClinical Solutions Wholesale2007-12-28Not applicableUs
Balsalazide Disodiumcapsule750 mg/1oralPhysicians Total Care, Inc.2010-08-18Not applicableUs
Balsalazide Disodiumcapsule750 mg/1oralAv Pak2014-11-06Not applicableUs
Balsalazide Disodiumcapsule750 mg/1oralMylan Pharmaceuticals Inc.2007-12-28Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ColazideNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Balsalazide disodium
ThumbNot applicableDBSALT000835
Categories
UNIIP80AL8J7ZP
CAS number80573-04-2
WeightAverage: 357.3175
Monoisotopic: 357.096085227
Chemical FormulaC17H15N3O6
InChI KeyInChIKey=IPOKCKJONYRRHP-FMQUCBEESA-N
InChI
InChI=1S/C17H15N3O6/c21-14-6-5-12(9-13(14)17(25)26)20-19-11-3-1-10(2-4-11)16(24)18-8-7-15(22)23/h1-6,9,21H,7-8H2,(H,18,24)(H,22,23)(H,25,26)/b20-19+
IUPAC Name
5-[(E)-2-{4-[(2-carboxyethyl)carbamoyl]phenyl}diazen-1-yl]-2-hydroxybenzoic acid
SMILES
OC(=O)CCNC(=O)C1=CC=C(C=C1)\N=N\C1=CC=C(O)C(=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as azobenzenes. These are organonitrogen aromatic compounds that contain a central azo group, where each nitrogen atom is conjugated to a bezene ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzobenzenes
Sub ClassNot Available
Direct ParentAzobenzenes
Alternative Parents
Substituents
  • Azobenzene
  • Beta amino acid or derivatives
  • Salicylic acid
  • Salicylic acid or derivatives
  • Hydroxybenzoic acid
  • Benzoic acid
  • Benzoic acid or derivatives
  • Benzamide
  • Benzoyl
  • Phenol
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Vinylogous acid
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azo compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of mildly to moderately active ulcerative colitis.
PharmacodynamicsBalsalazide is a prodrug that has little or no pharmacologic activity until it is enzymatically cleaved in the colon to produce mesalamine (5-aminosalicylic acid), an anti inflammatory drug indicated for the treatment of mildly to moderately active ulcerative colitis. Balsalazide disodium is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule, and the intert 4-aminobenzoyl-(beta)-alanine. As a result, the spectrum of pharmacologic activity of balsalazide is similar to that of mesalamine.
Mechanism of actionThe mechanism of action of 5-aminosalicylic acid is unknown, but appears exert its anti-inflammatory effects locally (in the GI tract) rather than systemically. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways (catalyzes the formation of prostaglandin precursors from arachidonic acid), and through the lipoxygenase pathways (catalyzes the formation of leukotrienes and hydroxyeicosatetraenoic acids from arachidonic acid and its metabolites), is increased in patients with chronic inflammatory bowel disease. Therefore, it is possible that 5-aminosalicylic acid diminishes inflammation by blocking production of arachidonic acid metabolites in the colon through both the inhibition of cyclooxygenase and lipoxygenase.
Related Articles
AbsorptionLow and variable, intact balsalazide is poorly absorbed systemically.
Volume of distributionNot Available
Protein binding≥99%
Metabolism

Cleaved in the colon via bacterial azoreduction to 5–aminosalicylic acid (5–ASA) and 4–aminobenzoyl-beta-alanine, the inactive carrier moiety.

SubstrateEnzymesProduct
Balsalazide
5-aminosalicylic acidDetails
Balsalazide
Not Available
4-aminobenzoyl-(beta)-alanineDetails
Route of eliminationThe products of the azoreduction of this compound, 5-ASA and 4-aminobenzoyl-ß-alanine, and their N-acetylated metabolites have been identified in plasma, urine and feces. Following single-dose administration of 2.25 g COLAZAL (three 750 mg capsules) under fasting conditions in healthy subjects, mean urinary recovery of balsalazide, 5-ASA, and N-Ac-5-ASA was 0.20%, 0.22% and 10.2%, respectively.
Half lifeHalf-life could not be determined.
ClearanceNot Available
ToxicityA single oral dose of balsalazide disodium at 5 grams/kg or 4-aminobenzoyl-(beta)-alanine, a metabolite of balsalazide disodium, at 1 gram/kg was non-lethal in mice and rats. No symptoms of acute toxicity were seen at these doses.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8947
Blood Brain Barrier+0.7807
Caco-2 permeable-0.6455
P-glycoprotein substrateNon-substrate0.6247
P-glycoprotein inhibitor INon-inhibitor0.7877
P-glycoprotein inhibitor IINon-inhibitor0.7615
Renal organic cation transporterNon-inhibitor0.8312
CYP450 2C9 substrateNon-substrate0.7932
CYP450 2D6 substrateNon-substrate0.8255
CYP450 3A4 substrateNon-substrate0.5523
CYP450 1A2 substrateNon-inhibitor0.7689
CYP450 2C9 inhibitorNon-inhibitor0.7883
CYP450 2D6 inhibitorNon-inhibitor0.8726
CYP450 2C19 inhibitorNon-inhibitor0.8153
CYP450 3A4 inhibitorNon-inhibitor0.9537
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9196
Ames testNon AMES toxic0.5593
CarcinogenicityNon-carcinogens0.75
BiodegradationNot ready biodegradable0.5575
Rat acute toxicity1.9986 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9148
hERG inhibition (predictor II)Non-inhibitor0.7772
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Apotex inc etobicoke site
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Salix pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Capsuleoral750 mg/1
Tabletoral1.1 g/1
Tablet, film coatedoral1.1 g/1
Prices
Unit descriptionCostUnit
Colazal 750 mg capsule2.82USD capsule
Balsalazide disodium 750 mg capsule1.54USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6197341 No1998-03-132018-03-13Us
US7452872 Yes2007-02-242027-02-24Us
US7625884 Yes2007-02-242027-02-24Us
US8497256 No2011-06-232031-06-23Us
US9192616 No2006-08-022026-08-02Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityFreely soluble as disodium saltNot Available
logP1.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0621 mg/mLALOGPS
logP3.37ALOGPS
logP3.17ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)3.06ChemAxon
pKa (Strongest Basic)-0.033ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area148.65 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity94.37 m3·mol-1ChemAxon
Polarizability35.98 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Eckardt C. G. Wolf, Nageib Mohamed, Bhaskar Reddy Guntoori, “Safe process for the preparation of balsalazide.” U.S. Patent US07271253, issued September 18, 2007.

US07271253
General References
  1. Wiggins JB, Rajapakse R: Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1279-84. doi: 10.1517/17425250903206996. [PubMed:19743890 ]
  2. Ragunath K, Williams JG: Review article: balsalazide therapy in ulcerative colitis. Aliment Pharmacol Ther. 2001 Oct;15(10):1549-54. [PubMed:11563993 ]
External Links
ATC CodesA07EC04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (44.9 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ArdeparinThe risk or severity of adverse effects can be increased when Balsalazide is combined with Ardeparin.
AzathioprineThe metabolism of Azathioprine can be decreased when combined with Balsalazide.
CelecoxibCelecoxib may increase the nephrotoxic activities of Balsalazide.
DalteparinThe risk or severity of adverse effects can be increased when Balsalazide is combined with Dalteparin.
DiclofenacDiclofenac may increase the nephrotoxic activities of Balsalazide.
DiflunisalDiflunisal may increase the nephrotoxic activities of Balsalazide.
DigoxinThe serum concentration of Digoxin can be decreased when it is combined with Balsalazide.
EnoxaparinThe risk or severity of adverse effects can be increased when Balsalazide is combined with Enoxaparin.
EtodolacEtodolac may increase the nephrotoxic activities of Balsalazide.
FenoprofenFenoprofen may increase the nephrotoxic activities of Balsalazide.
FloctafenineFloctafenine may increase the nephrotoxic activities of Balsalazide.
FlurbiprofenFlurbiprofen may increase the nephrotoxic activities of Balsalazide.
HeparinThe risk or severity of adverse effects can be increased when Balsalazide is combined with Heparin.
IbuprofenIbuprofen may increase the nephrotoxic activities of Balsalazide.
IndomethacinIndomethacin may increase the nephrotoxic activities of Balsalazide.
InfliximabInfliximab may increase the nephrotoxic activities of Balsalazide.
KetoprofenKetoprofen may increase the nephrotoxic activities of Balsalazide.
KetorolacKetorolac may increase the nephrotoxic activities of Balsalazide.
Mefenamic acidMefenamic acid may increase the nephrotoxic activities of Balsalazide.
MeloxicamMeloxicam may increase the nephrotoxic activities of Balsalazide.
MercaptopurineThe metabolism of Mercaptopurine can be decreased when combined with Balsalazide.
NabumetoneNabumetone may increase the nephrotoxic activities of Balsalazide.
NadroparinThe risk or severity of adverse effects can be increased when Balsalazide is combined with Nadroparin.
NaproxenNaproxen may increase the nephrotoxic activities of Balsalazide.
OxaprozinOxaprozin may increase the nephrotoxic activities of Balsalazide.
PiroxicamPiroxicam may increase the nephrotoxic activities of Balsalazide.
SulindacSulindac may increase the nephrotoxic activities of Balsalazide.
Tiaprofenic acidTiaprofenic acid may increase the nephrotoxic activities of Balsalazide.
TinzaparinThe risk or severity of adverse effects can be increased when Balsalazide is combined with Tinzaparin.
TioguanineThe metabolism of Tioguanine can be decreased when combined with Balsalazide.
TolmetinTolmetin may increase the nephrotoxic activities of Balsalazide.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation...
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
References
  1. Tursi A: Balsalazide in treating colonic diseases. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1555-63. doi: 10.1517/17425250903228842. [PubMed:19708827 ]
  2. Iacucci M, de Silva S, Ghosh S: Mesalazine in inflammatory bowel disease: a trendy topic once again? Can J Gastroenterol. 2010 Feb;24(2):127-33. [PubMed:20151072 ]
  3. Desreumaux P, Ghosh S: Review article: mode of action and delivery of 5-aminosalicylic acid - new evidence. Aliment Pharmacol Ther. 2006 Sep;24 Suppl 1:2-9. [PubMed:16939423 ]
  4. Linard C, Gremy O, Benderitter M: Reduction of peroxisome proliferation-activated receptor gamma expression by gamma-irradiation as a mechanism contributing to inflammatory response in rat colon: modulation by the 5-aminosalicylic acid agonist. J Pharmacol Exp Ther. 2008 Mar;324(3):911-20. Epub 2007 Dec 12. [PubMed:18077625 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
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:17139284 ]
  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:17016423 ]
  3. Wiggins JB, Rajapakse R: Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1279-84. doi: 10.1517/17425250903206996. [PubMed:19743890 ]
  4. Stolfi C, Fina D, Caruso R, Caprioli F, Sarra M, Fantini MC, Rizzo A, Pallone F, Monteleone G: Cyclooxygenase-2-dependent and -independent inhibition of proliferation of colon cancer cells by 5-aminosalicylic acid. Biochem Pharmacol. 2008 Feb 1;75(3):668-76. Epub 2007 Sep 29. [PubMed:17981262 ]
  5. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. [PubMed:12950415 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
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:17139284 ]
  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:17016423 ]
  3. Wiggins JB, Rajapakse R: Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1279-84. doi: 10.1517/17425250903206996. [PubMed:19743890 ]
  4. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. [PubMed:12950415 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Iron ion binding
Specific Function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular Weight:
77982.595 Da
References
  1. Wiggins JB, Rajapakse R: Balsalazide: a novel 5-aminosalicylate prodrug for the treatment of active ulcerative colitis. Expert Opin Drug Metab Toxicol. 2009 Oct;5(10):1279-84. doi: 10.1517/17425250903206996. [PubMed:19743890 ]
  2. Rask-Madsen J, Bukhave K, Laursen LS, Lauritsen K: 5-Lipoxygenase inhibitors for the treatment of inflammatory bowel disease. Agents Actions. 1992;Spec No:C37-46. [PubMed:1359745 ]

Enzymes

Kind
Protein
Organism
Bacillus sp. (strain OY1-2)
Pharmacological action
unknown
Actions
substrate
General Function:
Azobenzene reductase activity
Specific Function:
Catalyzes the reductive cleavage of azo bond in aromatic azo compounds to the corresponding amines. Requires NADPH as an electron donor for its activity. Compounds with paired naphthalene groups coupled with the azo group are good substrates, with the following preference order: Rocceline > Sumifix Black B > Solar Orange.
Gene Name:
azr
Uniprot ID:
Q9FAW5
Molecular Weight:
19293.155 Da
References
  1. Ragunath K, Williams JG: Review article: balsalazide therapy in ulcerative colitis. Aliment Pharmacol Ther. 2001 Oct;15(10):1549-54. [PubMed:11563993 ]
  2. Ryan A, Laurieri N, Westwood I, Wang CJ, Lowe E, Sim E: A novel mechanism for azoreduction. J Mol Biol. 2010 Jul 2;400(1):24-37. doi: 10.1016/j.jmb.2010.04.023. Epub 2010 Apr 24. [PubMed:20417637 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on June 26, 2016 03:07