Olsalazine
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
Structure for Olsalazine (DB01250)
- 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 Dipentum Capsule 250 mg Oral Atnahs Pharma Uk Limited 1995-12-31 Not applicable Canada 
Dipentum Capsule, gelatin coated 250 mg/1 Oral Carilion Materials Management 2015-05-15 Not applicable US 
Dipentum Capsule, gelatin coated 250 mg/1 Oral Carilion Materials Management 1990-07-31 Not applicable US Dipentum Capsule, gelatin coated 250 mg/1 Oral MEDA Pharmaceuticals 2015-05-15 Not applicable US Dipentum Capsule 250 mg/1 Oral Ucb Inc 2007-10-03 Not applicable US Dipentum Capsule, gelatin coated 250 mg/1 Oral Alaven Pharmaceutical 1990-07-31 2017-05-11 US - International/Other Brands
- Dipentum
- Categories
- Acids, Carbocyclic
- Agents causing hyperkalemia
- Agents that produce hypertension
- Alimentary Tract and Metabolism
- Aminosalicylate
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Benzene Derivatives
- Benzoates
- Central Nervous System Agents
- Gastrointestinal Agents
- Hydroxy Acids
- Hydroxybenzoates
- Intestinal Antiinflammatory Agents
- Nephrotoxic agents
- Peripheral Nervous System Agents
- Phenols
- Salicylates
- Sensory System Agents
- 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.
Target Actions Organism AThiopurine S-methyltransferase inhibitorHumans AInterferon gamma Not Available Humans - 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
Drug Interaction (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-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Olsalazine is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid. 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. 3,4-Methylenedioxyamphetamine The risk or severity of hypertension can be increased when Olsalazine is combined with 3,4-Methylenedioxyamphetamine. 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. - 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
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/1 Capsule Oral 250 mg 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
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 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
- 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]
- 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 February 22, 2019 22:55