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Identification
NameOlsalazine
Accession NumberDB01250
TypeSmall Molecule
GroupsApproved
Description

Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. Olsalazine is a derivative of salicylic acid. Inactive by itself (it is a prodrug), it is converted by the bacteria in the colon to mesalamine. Mesalamine works as an anti-inflammatory agent in treating inflammatory diseases of the intestines.

Structure
Thumb
Synonyms
Dipentum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dipentumcapsule, gelatin coated250 mg/1oralMEDA Pharmaceuticals2015-05-15Not applicableUs
Dipentumcapsule250 mgoralAtnahs Pharma Uk Limited1995-12-31Not applicableCanada
Dipentumcapsule, gelatin coated250 mg/1oralAlaven Pharmaceutical LLC1990-07-31Not applicableUs
Dipentumcapsule, gelatin coated250 mg/1oralCarilion Materials Management1990-07-31Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Olsalazine sodium
6054-98-4
Thumb
  • InChI Key: QQWFSVYVHLECFP-XBPUGJBTSA-L
  • Monoisotopic Mass: 346.017775348
  • Average Mass: 346.2027
DBSALT000191
Categories
UNIIULS5I8J03O
CAS number15722-48-2
WeightAverage: 302.239
Monoisotopic: 302.053886062
Chemical FormulaC14H10N2O6
InChI KeyInChIKey=QQBDLJCYGRGAKP-FOCLMDBBSA-N
InChI
InChI=1S/C14H10N2O6/c17-11-3-1-7(5-9(11)13(19)20)15-16-8-2-4-12(18)10(6-8)14(21)22/h1-6,17-18H,(H,19,20)(H,21,22)/b16-15+
IUPAC Name
5-[(E)-2-(3-carboxy-4-hydroxyphenyl)diazen-1-yl]-2-hydroxybenzoic acid
SMILES
OC(=O)C1=CC(=CC=C1O)\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
  • Salicylic acid
  • Salicylic acid or derivatives
  • Hydroxybenzoic acid
  • Benzoic acid
  • Benzoic acid or derivatives
  • Benzoyl
  • Phenol
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Vinylogous acid
  • 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 DescriptorsNot Available
Pharmacology
IndicationFor the treatment of Inflammatory Bowel Disease and Ulcerative Colitis.
PharmacodynamicsOlsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. Olsalazine reduces the bowel inflammation, diarrhea (stool frequency), rectal bleeding, and abdominal pain. Like Balsalazide, Olsalazine is believed to deliver Mesalazine, or 5-aminosalicylic acid (5-ASA), past the small intestine, directly to the large intestine, which is that active site of disease in ulcerative colitis.
Mechanism of actionOrally administered olsalazine is converted to mesalamine which is thought to be the therapeutically active agent in the treatment of ulcerative colitis. The mechanism of action of mesalamine (and sulfasalazine) is unknown, but appears to be topical rather than systemic. Mucosal production of arachidonic acid (AA) metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes (LTs) and hydroxyelcosatetraenoic acids (HETEs) is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin (PG) production in the colon.
Related Articles
AbsorptionAfter oral administration, olsalazine, has limited systemic bioavailability. 98-99% of the dose is converted to mesalamine (5-ASA) in the colon, which is absorbed slowly resulting in very high local concentrations in the colon.
Volume of distributionNot Available
Protein bindingOlsalazine and olsalazine-S are more than 99% bound to plasma proteins. Mesalamine (5-ASA) is 74% bound to plasma proteins.
Metabolism

Most (98 to 99%) of an oral dose is rapidly converted into two molecules of 5-aminosalicylic acid (5-ASA) by colonic bacteria and the low prevailing redox potential found in this environment. The conversion of olsalazine to mesalamine in the colon is similar to that of sulfasalazine, which is converted into sulfapyridine and mesalamine. Approximately 0.1% of an oral dose of olsalazine is metabolized in the liver to olsalazine-O-sulfate (olsalazine-S)

SubstrateEnzymesProduct
Olsalazine
Not Available
Olsalazine-O-sulfateDetails
Route of eliminationApproximately 0.1% of an oral dose of olsalazine is metabolized in the liver to olsalazine-O-sulfate (olsalazine-S).The remaining 5-ASA is partially acetylated and is excreted in the feces.
Half lifeOlsalazine has an elimination half-life of 0.9 hours, however, olsalazine-S has a half-life of 7 days.
ClearanceNot Available
ToxicityMaximum single oral doses of 5g/kg in mice and rats and 2 g/kg in dogs were not lethal.
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+0.8502
Blood Brain Barrier+0.6279
Caco-2 permeable-0.6449
P-glycoprotein substrateNon-substrate0.7433
P-glycoprotein inhibitor INon-inhibitor0.8628
P-glycoprotein inhibitor IINon-inhibitor0.9525
Renal organic cation transporterNon-inhibitor0.8844
CYP450 2C9 substrateNon-substrate0.7774
CYP450 2D6 substrateNon-substrate0.8748
CYP450 3A4 substrateNon-substrate0.6636
CYP450 1A2 substrateNon-inhibitor0.8006
CYP450 2C9 inhibitorNon-inhibitor0.7804
CYP450 2D6 inhibitorNon-inhibitor0.9047
CYP450 2C19 inhibitorNon-inhibitor0.8638
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8912
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.5546
BiodegradationNot ready biodegradable0.8701
Rat acute toxicity1.4882 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9506
hERG inhibition (predictor II)Non-inhibitor0.9453
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral250 mg
Capsule, gelatin coatedoral250 mg/1
Prices
Unit descriptionCostUnit
Dipentum 250 mg capsule1.8USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting pointSodium salt decomposes at 240 °CNot Available
logP2.3Not Available
Caco2 permeability-6.96ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0781 mg/mLALOGPS
logP2.77ALOGPS
logP4.39ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)2.93ChemAxon
pKa (Strongest Basic)-0.019ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area139.78 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity78.85 m3·mol-1ChemAxon
Polarizability28.61 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 ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesA07EC03
AHFS Codes
  • 56:36.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
ArdeparinThe risk or severity of adverse effects can be increased when Olsalazine is combined with Ardeparin.
DigoxinThe serum concentration of Digoxin can be decreased when it is combined with Olsalazine.
HeparinThe risk or severity of adverse effects can be increased when Olsalazine is combined with Heparin.
InfliximabInfliximab may increase the nephrotoxic activities of Olsalazine.
TioguanineThe metabolism of Tioguanine can be decreased when combined with Olsalazine.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Thiopurine s-methyltransferase activity
Specific Function:
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.
Gene Name:
TPMT
Uniprot ID:
P51580
Molecular Weight:
28180.09 Da
References
  1. Lewis LD, Benin A, Szumlanski CL, Otterness DM, Lennard L, Weinshilboum RM, Nierenberg DW: Olsalazine and 6-mercaptopurine-related bone marrow suppression: a possible drug-drug interaction. Clin Pharmacol Ther. 1997 Oct;62(4):464-75. [PubMed:9357398 ]
  2. Lennard L: TPMT in the treatment of Crohn's disease with azathioprine. Gut. 2002 Aug;51(2):143-6. [PubMed:12117866 ]
  3. Lennard L: Clinical implications of thiopurine methyltransferase--optimization of drug dosage and potential drug interactions. Ther Drug Monit. 1998 Oct;20(5):527-31. [PubMed:9780130 ]
  4. Shipkova M, Niedmann PD, Armstrong VW, Oellerich M, Wieland E: Determination of thiopurine methyltransferase activity in isolated human erythrocytes does not reflect putative in vivo enzyme inhibition by sulfasalazine. Clin Chem. 2004 Feb;50(2):438-41. [PubMed:14752016 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
General Function:
Interferon-gamma receptor binding
Specific Function:
Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.
Gene Name:
IFNG
Uniprot ID:
P01579
Molecular Weight:
19348.165 Da
References
  1. Egan LJ, Sandborn WJ: Inhibition of nuclear factor kappaB by sulfasalazine: a new target for inflammatory bowel disease therapy? Gastroenterology. 1998 Nov;115(5):1295-6. [PubMed:9797390 ]
  2. Ito R, Shin-Ya M, Kishida T, Urano A, Takada R, Sakagami J, Imanishi J, Kita M, Ueda Y, Iwakura Y, Kataoka K, Okanoue T, Mazda O: Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice. Clin Exp Immunol. 2006 Nov;146(2):330-8. [PubMed:17034586 ]
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Drug created on March 30, 2007 06:25 / Updated on January 15, 2016 17:38