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

Similar Structures

Synonyms

Olsalazine

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Olsalazine sodium	Y7JEW0XG7I	6054-98-4	QQWFSVYVHLECFP-XBPUGJBTSA-L

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Dipentum	Capsule	250 mg/1	Oral	Ucb Inc	2007-10-03	Not applicable
Dipentum	Capsule, gelatin coated	250 mg/1	Oral	MEDA Pharmaceuticals	2015-05-15	Not applicable
Dipentum	Capsule	250 mg	Oral	Atnahs Pharma Uk Limited	1995-12-31	Not applicable
Dipentum	Capsule, gelatin coated	250 mg/1	Oral	Alaven Pharmaceutical	1990-07-31	2017-05-11
Dipentum	Capsule, gelatin coated	250 mg/1	Oral	Carilion Materials Management	2015-05-15	Not applicable
Dipentum	Capsule, gelatin coated	250 mg/1	Oral	Carilion Materials Management	1990-07-31	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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

Ulcerative Colitis (UC)

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. Olsalazine is thought to work like balsalazide, delivering mesalazine or 5-aminosalicylic acid past the small intestine to the large intestine to act on the site of disease.

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.

Target	Actions	Organism
AThiopurine S-methyltransferase	inhibitor	Humans
AInterferon gamma	Not Available	Humans

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Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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)

Olsalazine
Olsalazine-O-sulfate

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

Drug	Interaction
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(R)-warfarin	The risk or severity of bleeding can be increased when Olsalazine is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of bleeding can be increased when Olsalazine is combined with (S)-Warfarin.
1-benzylimidazole	The risk or severity of hypertension can be increased when Olsalazine is combined with 1-benzylimidazole.
2,4-thiazolidinedione	Olsalazine may increase the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine	The risk or severity of hypertension can be increased when Olsalazine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of hypertension can be increased when Olsalazine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,5-diiodothyropropionic acid	The therapeutic efficacy of 3,5-diiodothyropropionic acid can be increased when used in combination with Olsalazine.
3,5-Diiodotyrosine	The therapeutic efficacy of 3,5-Diiodotyrosine can be increased when used in combination with Olsalazine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of hypertension can be increased when Olsalazine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarin	The risk or severity of bleeding can be increased when Olsalazine is combined with 4-hydroxycoumarin.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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
Wikipedia: Olsalazine

ATC Codes

A07EC03 — Olsalazine

AHFS Codes

56:36.00 — Anti-inflammatory Agents

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Completed	Treatment	Ankylosing Spondylitis (AS)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Alaven Pharmaceutical
Pfizer Inc.
Pharmacia Inc.
UCB Pharma

Dosage forms

Form	Route	Strength
Capsule	Oral	250 mg
Capsule	Oral	250 mg/1
Capsule, gelatin coated	Oral	250 mg/1

Prices

Unit description	Cost	Unit
Dipentum 250 mg capsule	1.8USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	Sodium salt decomposes at 240 °C	Not Available
logP	2.3	Not Available
Caco2 permeability	-6.96	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.0781 mg/mL	ALOGPS
logP	2.77	ALOGPS
logP	4.39	ChemAxon
logS	-3.6	ALOGPS
pKa (Strongest Acidic)	2.93	ChemAxon
pKa (Strongest Basic)	-0.019	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	8	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	139.78 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	78.85 m³·mol^-1	ChemAxon
Polarizability	28.61 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.8502
Blood Brain Barrier	+	0.6279
Caco-2 permeable	-	0.6449
P-glycoprotein substrate	Non-substrate	0.7433
P-glycoprotein inhibitor I	Non-inhibitor	0.8628
P-glycoprotein inhibitor II	Non-inhibitor	0.9525
Renal organic cation transporter	Non-inhibitor	0.8844
CYP450 2C9 substrate	Non-substrate	0.7774
CYP450 2D6 substrate	Non-substrate	0.8748
CYP450 3A4 substrate	Non-substrate	0.6636
CYP450 1A2 substrate	Non-inhibitor	0.8006
CYP450 2C9 inhibitor	Non-inhibitor	0.7804
CYP450 2D6 inhibitor	Non-inhibitor	0.9047
CYP450 2C19 inhibitor	Non-inhibitor	0.8638
CYP450 3A4 inhibitor	Non-inhibitor	0.8309
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8912
Ames test	Non AMES toxic	0.9132
Carcinogenicity	Non-carcinogens	0.5546
Biodegradation	Not ready biodegradable	0.8701
Rat acute toxicity	1.4882 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9506
hERG inhibition (predictor II)	Non-inhibitor	0.9453

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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
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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

Details1. Thiopurine S-methyltransferase

Kind: Protein
Organism: Humans
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

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]
Lennard L: TPMT in the treatment of Crohn's disease with azathioprine. Gut. 2002 Aug;51(2):143-6. [PubMed:12117866]
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]
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]

Details2. Interferon gamma

Kind: Protein
Organism: Humans
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

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]
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 July 18, 2019 18:59

Olsalazine

Identification

Structure for Olsalazine (DB01250)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References