Balsalazide

Identification

Summary

Balsalazide is an aminosalicylate used to treat ulcerative colitis.

Brand Names
Colazal
Generic Name
Balsalazide
DrugBank Accession Number
DB01014
Background

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 works by deliverying mesalazine to the large intestine to act directly on ulcerative colitis. Mesalazine is also known as 5-aminosalicylic acid, or 5-ASA.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 357.3175
Monoisotopic: 357.096085227
Chemical Formula
C17H15N3O6
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
  • Balsalazide
  • Balsalazidum

Pharmacology

Indication

For the treatment of mildly to moderately active ulcerative colitis.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMild ulcerative colitis••••••••••••••••••• •••• ••••••
Treatment ofModerate ulcerative colitis••••••••••••••••••• •••• ••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Balsalazide 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 action

The 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.

TargetActionsOrganism
APeroxisome proliferator-activated receptor gamma
agonist
Humans
AProstaglandin G/H synthase 2
inhibitor
Humans
AProstaglandin G/H synthase 1
inhibitor
Humans
AArachidonate 5-lipoxygenase
inhibitor
Humans
Absorption

Low and variable, intact balsalazide is poorly absorbed systemically.

Volume of distribution

Not 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.

Hover over products below to view reaction partners

Route of elimination

The 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-life

Half-life could not be determined.

Clearance

Not Available

Adverse Effects
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Toxicity

A 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.

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.
DrugInteraction
AbacavirBalsalazide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Balsalazide is combined with Abciximab.
AcarboseBalsalazide may increase the hypoglycemic activities of Acarbose.
AcebutololBalsalazide may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Balsalazide can be decreased when used in combination with Aceclofenac.
Food Interactions
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Balsalazide disodium1XL6BJI034150399-21-6XDCNKOBSQURQOZ-MVIJUDHYSA-L
Product Images
International/Other Brands
Colazide
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ColazalCapsule750 mg/1OralSalix Pharmaceuticals, Inc2000-07-18Not applicableUS flag
ColazalCapsule750 mg/1OralPhysicians Total Care, Inc.2005-06-092011-06-30US flag
ColazalCapsule750 mg/1OralCardinal Health2000-07-182010-02-28US flag
GiazoTablet, film coated1.1 g/1OralSalix Pharmaceuticals, Inc2012-02-032020-08-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Balsalazide DisodiumCapsule750 mg/1OralGolden State Medical Supply, Inc.2007-12-28Not applicableUS flag
Balsalazide DisodiumCapsule750 mg/1OralAmerincan Health Packaging2014-07-272018-07-31US flag
Balsalazide DisodiumTablet1.1 g/1OralPar Pharmaceutical Inc.2015-09-082015-09-08US flag
Balsalazide DisodiumCapsule750 mg/1OralPhysicians Total Care, Inc.2010-08-18Not applicableUS flag
Balsalazide DisodiumCapsule750 mg/1OralOceanside Pharmaceuticals2000-07-18Not applicableUS flag

Categories

ATC Codes
A07EC04 — Balsalazide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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 benzene ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azobenzenes
Sub Class
Not Available
Direct Parent
Azobenzenes
Alternative Parents
Beta amino acids and derivatives / Salicylic acids / Benzamides / Benzoic acids / Benzoyl derivatives / 1-hydroxy-2-unsubstituted benzenoids / Dicarboxylic acids and derivatives / Vinylogous acids / Secondary carboxylic acid amides / Azo compounds
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Substituents
1-hydroxy-2-unsubstituted benzenoid / Aromatic homomonocyclic compound / Azo compound / Azobenzene / Benzamide / Benzenoid / Benzoic acid / Benzoic acid or derivatives / Benzoyl / Beta amino acid or derivatives
show 21 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monohydroxybenzoic acid (CHEBI:267413)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
P80AL8J7ZP
CAS number
80573-04-2
InChI Key
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-[(1E)-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

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. [Article]
  2. Ragunath K, Williams JG: Review article: balsalazide therapy in ulcerative colitis. Aliment Pharmacol Ther. 2001 Oct;15(10):1549-54. [Article]
  3. FDA Approved Drug Products: Colazal (basalazide disodium) capsules for oral use [Link]
Human Metabolome Database
HMDB0015149
KEGG Drug
D07488
PubChem Compound
6335412
PubChem Substance
46505592
ChemSpider
10662422
RxNav
18747
ChEBI
267413
ChEMBL
CHEMBL1201346
ZINC
ZINC000003952881
Therapeutic Targets Database
DAP000733
PharmGKB
PA448536
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Balsalazide
FDA label
Download (44.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedSupportive CareInflammatory Bowel Diseases (IBD) / Ulcerative Colitis1
3CompletedTreatmentInflammatory Bowel Diseases (IBD) / Ulcerative Colitis1
1CompletedNot AvailableHealthy Volunteers (HV)2
Not AvailableCompletedTreatmentUlcerative Colitis2

Pharmacoeconomics

Manufacturers
  • Apotex inc etobicoke site
  • Mylan pharmaceuticals inc
  • Roxane laboratories inc
  • Salix pharmaceuticals inc
Packagers
  • Apotex Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Salix Pharmaceuticals
Dosage Forms
FormRouteStrength
CapsuleOral750 mg/1
TabletOral1.1 g/1
CapsuleOral750 MG
CapsuleOral
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)Region
US7452872Yes2008-11-182027-02-24US flag
US7625884Yes2009-12-012027-02-24US flag
US6197341No2001-03-062018-03-13US flag
US8497256No2013-07-302031-06-23US flag
US9192616No2015-11-242026-08-02US flag

Properties

State
Solid
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 RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0ldi-1393000000-af92622c6ce32e802a99
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0gb9-0090000000-3efeb84ef93c25381028
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4r-0019000000-4402ebfff105ce6e520d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0090000000-75df5afb51977a88b7ec
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-1092000000-e949a91a57799829c879
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0391000000-f293b03350c3d35e0aa4
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-1290000000-b9b4baedb768cdf2e34c
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-195.7574324
predicted
DarkChem Lite v0.1.0
[M-H]-195.7941324
predicted
DarkChem Lite v0.1.0
[M-H]-183.05284
predicted
DeepCCS 1.0 (2019)
[M+H]+191.2576324
predicted
DarkChem Lite v0.1.0
[M+H]+191.7883324
predicted
DarkChem Lite v0.1.0
[M+H]+185.41084
predicted
DeepCCS 1.0 (2019)
[M+Na]+191.4727324
predicted
DarkChem Lite v0.1.0
[M+Na]+192.13875
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
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...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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 gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Arachidonate 5-lipoxygenase
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. [Article]
  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. [Article]

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 co...
Gene Name
azr
Uniprot ID
Q9FAW5
Uniprot Name
NADPH azoreductase
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. [Article]
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2024 02:34