Identification

Name
Olsalazine
Accession Number
DB01250
Type
Small Molecule
Groups
Approved
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
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Olsalazine sodiumY7JEW0XG7I6054-98-4QQWFSVYVHLECFP-XBPUGJBTSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DipentumCapsule, gelatin coated250 mg/1OralMeda Pharmaceuticals Ltd2015-05-15Not applicableUs
DipentumCapsule250 mgOralAtnahs Pharma Uk Limited1995-12-31Not applicableCanada
DipentumCapsule, gelatin coated250 mg/1OralAlaven Pharmaceutical1990-07-312017-05-11Us
DipentumCapsule, gelatin coated250 mg/1OralCarilion Materials Management1990-07-31Not applicableUs
DipentumCapsule, gelatin coated250 mg/1OralCarilion Materials Management2015-05-15Not applicableUs
DipentumCapsule250 mg/1OralUcb Inc2007-10-03Not applicableUs
International/Other Brands
Dipentum
Categories
UNII
ULS5I8J03O
CAS number
15722-48-2
Weight
Average: 302.239
Monoisotopic: 302.053886062
Chemical Formula
C14H10N2O6
InChI Key
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

Pharmacology

Indication

For the treatment of Inflammatory Bowel Disease and Ulcerative Colitis.

Associated Conditions
Pharmacodynamics

Olsalazine 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 action

Orally 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.

TargetActionsOrganism
AThiopurine S-methyltransferase
inhibitor
Human
AInterferon gammaNot AvailableHuman
Absorption

After 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 distribution
Not Available
Protein binding

Olsalazine 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)

Route of elimination

Approximately 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 life

Olsalazine has an elimination half-life of 0.9 hours, however, olsalazine-S has a half-life of 7 days.

Clearance
Not Available
Toxicity

Maximum 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Olsalazine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Olsalazine is combined with (S)-Warfarin.
2,4-thiazolidinedioneOlsalazine may increase the hypoglycemic activities of 2,4-thiazolidinedione.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Olsalazine is combined with 4-hydroxycoumarin.
AbacavirOlsalazine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding can be increased when Olsalazine is combined with Abciximab.
AcarboseOlsalazine may increase the hypoglycemic activities of Acarbose.
AcebutololOlsalazine may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Olsalazine is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Olsalazine is combined with Acemetacin.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015380
KEGG Drug
D00727
KEGG Compound
C07323
PubChem Compound
6003770
PubChem Substance
46506356
ChemSpider
10642377
ChEMBL
CHEMBL425
PharmGKB
PA450700
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Olsalazine
ATC Codes
A07EC03 — Olsalazine
AHFS Codes
  • 56:36.00 — Anti-inflammatory Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAnkylosing Spondylitis (AS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alaven Pharmaceutical
  • Pfizer Inc.
  • Pharmacia Inc.
  • UCB Pharma
Dosage forms
FormRouteStrength
CapsuleOral250 mg
CapsuleOral250 mg/1
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Sodium 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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Salicylic acids / Benzoic acids / Benzoyl derivatives / 1-hydroxy-2-unsubstituted benzenoids / Dicarboxylic acids and derivatives / Vinylogous acids / Azo compounds / Propargyl-type 1,3-dipolar organic compounds / Carboxylic acids / Organopnictogen compounds
show 3 more
Substituents
Azobenzene / Hydroxybenzoic acid / Salicylic acid or derivatives / Salicylic acid / Benzoic acid or derivatives / Benzoic acid / Benzoyl / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Monocyclic benzene moiety
show 16 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not 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
Uniprot Name
Thiopurine S-methyltransferase
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 macrop...
Gene Name
IFNG
Uniprot ID
P01579
Uniprot Name
Interferon gamma
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]

Drug created on March 30, 2007 06:25 / Updated on November 14, 2018 12:51