Identification
- Summary
Eluxadoline is a mixed mu-opioid receptor agonist used to treat irritable bowel syndrome with diarrhea.
- Brand Names
- Viberzi
- Generic Name
- Eluxadoline
- DrugBank Accession Number
- DB09272
- Background
Eluxadoline is a mixed mu-opioid receptor agonist, kappa-opioid receptor agonist, and a-delta opioid receptor antagonist indicated for use in diarrhea-predominant irritable bowel syndrome (IBS-D). The mu-, kappa-, and delta-opioid receptors mediate endogenous and exogenous opioid response in the central nervous system and peripherally in the gastrointestinal system. Agonism of peripheral mu-opioid receptors results in reduced colonic motility, while antagonism of central delta-opioid receptors results in improved analgesia, making eluxadoline usable for the symptoms of both pain and diarrhea characteristic of IBS-D.
Marketed under the tradename Viberzi (FDA), eluxadoline is an antimotility agent that decreases bowel contractions, inhibits colonic transit, and reduces fluid/ion secretion resulting in improved symptoms of abdominal pain and reductions in the Bristol Stool Scale.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Eluxadoline (DB09272)
- Weight
- Average: 569.662
Monoisotopic: 569.263819247 - Chemical Formula
- C32H35N5O5
- Synonyms
- 5-({(4-carbamoyl-2,6-dimethyl-L-phenylalanyl)[(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]amino}methyl)-2-methoxybenzoic acid
- Eluxadoline
- External IDs
- JNJ 27018966
- JNJ-27018966
- JNJ27018966
Pharmacology
- Indication
For the treatment of irritable bowel syndrome with diarrhea (IBS-D).
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
Eluxadoline is a mu-opioid receptor agonis, kappa opioid receptor agonist and a delta opioid receptor antagonist. Eluxadoline is used for diarrhea predominant IBS because it reduces intestinal contractility and normalizes stress-induced acceleration of upper GI transit. Antagonistic activity at the delta receptor minimizes the constipating effect usually seen by mu-opioid receptor agonists alone. Because of it's limited systemic bioavailability, there may be less side effects associated with the use of eluxadoline in comparison with other therapies used to treat diarrhea predominant IBS.
Target Actions Organism AMu-type opioid receptor agonistHumans ADelta-type opioid receptor antagonistHumans AKappa-type opioid receptor agonistHumans - Absorption
The oral absorption of eluxadoline is poor - estimated to be 1.02%, this could be attributed to poor in vitro GI permeability, and its zwitterionic nature leading to a negatively charged molecule across the GI pH range.
- Volume of distribution
Not Available
- Protein binding
81%
- Metabolism
The metabolism of eluxadoline is currently unclear, however evidence suggests limited glucoronidation forms an acyl glucuronide metabolite that is then excreted into urine.
- Route of elimination
82% excreted in feces, <1% excreted in urine.
- Half-life
The mean plasma elimination half-life ranged from 3.7 hours to 6 hours.
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most common adverse reactions (>5%) are constipation, nausea and abdominal pain.
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Eluxadoline is combined with 1,2-Benzodiazepine. Acetazolamide The therapeutic efficacy of Acetazolamide can be decreased when used in combination with Eluxadoline. Acetophenazine The risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Eluxadoline. Acetylcysteine The serum concentration of Eluxadoline can be increased when it is combined with Acetylcysteine. Acetylsalicylic acid The excretion of Eluxadoline can be decreased when combined with Acetylsalicylic acid. Aclidinium The risk or severity of constipation can be increased when Aclidinium is combined with Eluxadoline. Acyclovir The excretion of Eluxadoline can be decreased when combined with Acyclovir. Alfentanil The risk or severity of constipation can be increased when Alfentanil is combined with Eluxadoline. Alimemazine The risk or severity of hypotension and CNS depression can be increased when Alimemazine is combined with Eluxadoline. Alloin The therapeutic efficacy of Alloin can be decreased when used in combination with Eluxadoline. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Avoid excessive or chronic alcohol consumption. The risk of pancreatitis is increased with excess/chronic alcohol consumption.
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Truberzi Tablet, film coated 100 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2021-02-25 EU 
Truberzi Tablet, film coated 75 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2021-02-25 EU Truberzi Tablet, film coated 75 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2021-02-25 EU Truberzi Tablet, film coated 100 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2021-02-25 EU Truberzi Tablet, film coated 75 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2021-02-25 EU Truberzi Tablet, film coated 100 mg Oral Allergan Pharmaceuticals International Limited 2020-12-16 2021-02-25 EU Viberzi Tablet 100 mg Oral Allergan 2017-04-24 Not applicable Canada 
Viberzi Tablet, film coated 75 mg/1 Oral Allergan, Inc. 2015-10-01 Not applicable US 
Viberzi Tablet 75 mg Oral Allergan 2017-04-24 Not applicable Canada Viberzi Tablet, film coated 100 mg/1 Oral Allergan, Inc. 2015-10-01 Not applicable US
Categories
- ATC Codes
- A07DA06 — Eluxadoline
- Drug Categories
- Alimentary Tract and Metabolism
- Amino Acids
- Amino Acids, Aromatic
- Amino Acids, Cyclic
- Amino Acids, Peptides, and Proteins
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Antipropulsives
- Gastrointestinal Agents
- Miscellaneous GI Drugs
- Mixed Agonist / Antagonist Opioids
- mu-Opioid Receptor Agonist
- OAT3/SLC22A8 Substrates
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B1/SLCO1B1 Substrates
- Opioid Antagonists
- Opioids
- Receptors, Opioid, delta, antagonists & inhibitors
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Phenylalanine and derivatives
- Alternative Parents
- Alpha amino acid amides / Phenylimidazoles / O-methoxybenzoic acids and derivatives / Amphetamines and derivatives / Benzamides / Benzoic acids / m-Xylenes / Benzoyl derivatives / Anisoles / Imidazolyl carboxylic acids and derivatives show 16 more
- Substituents
- 4-phenylimidazole / 5-phenylimidazole / Alkyl aryl ether / Alpha-amino acid amide / Amine / Amino acid / Amphetamine or derivatives / Anisole / Aralkylamine / Aromatic heteromonocyclic compound show 35 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- amino acid amide, imidazoles, benzamides, L-phenylalanine derivative, methoxybenzoic acid (CHEBI:85980)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 45TPJ4MBQ1
- CAS number
- 864821-90-9
- InChI Key
- QFNHIDANIVGXPE-FNZWTVRRSA-N
- InChI
- InChI=1S/C32H35N5O5/c1-18-12-23(29(34)38)13-19(2)24(18)15-26(33)31(39)37(17-21-10-11-28(42-4)25(14-21)32(40)41)20(3)30-35-16-27(36-30)22-8-6-5-7-9-22/h5-14,16,20,26H,15,17,33H2,1-4H3,(H2,34,38)(H,35,36)(H,40,41)/t20-,26-/m0/s1
- IUPAC Name
- 5-{[(2S)-2-amino-3-(4-carbamoyl-2,6-dimethylphenyl)-N-[(1S)-1-(4-phenyl-1H-imidazol-2-yl)ethyl]propanamido]methyl}-2-methoxybenzoic acid
- SMILES
- COC1=CC=C(CN([C@@H](C)C2=NC(=CN2)C2=CC=CC=C2)C(=O)[C@@H](N)CC2=C(C)C=C(C=C2C)C(N)=O)C=C1C(O)=O
References
- Synthesis Reference
Breslin HJ, Diamond CJ, Kavash RW, Cai C, Dyatkin AB, Miskowski TA, Zhang SP, Wade PR, Hornby PJ, He W: Identification of a dual delta OR antagonist/mu OR agonist as a potential therapeutic for diarrhea-predominant Irritable Bowel Syndrome (IBS-d). Bioorg Med Chem Lett. 2012 Jul 15;22(14):4869-72. doi: 10.1016/j.bmcl.2012.05.042. Epub 2012 May 24. Pubmed
- General References
- Garnock-Jones KP: Eluxadoline: First Global Approval. Drugs. 2015 Jul;75(11):1305-10. doi: 10.1007/s40265-015-0436-4. [Article]
- Nee J, Zakari M, Lembo AJ: Current and emerging drug options in the treatment of diarrhea predominant irritable bowel syndrome. Expert Opin Pharmacother. 2015 Dec;16(18):2781-92. doi: 10.1517/14656566.2015.1101449. Epub 2015 Nov 11. [Article]
- Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS: Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9. [Article]
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
- Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA: Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014 Dec 1;92(3):448-56. doi: 10.1016/j.bcp.2014.09.015. Epub 2014 Sep 28. [Article]
- FDA Approved Drug Products: VIBERZI (eluxadoline) tablets [Link]
- External Links
- KEGG Drug
- D10403
- PubChem Compound
- 11250029
- PubChem Substance
- 310265167
- ChemSpider
- 9425062
- BindingDB
- 50393720
- 1653781
- ChEBI
- 85980
- ChEMBL
- CHEMBL2159122
- ZINC
- ZINC000014210876
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Eluxadoline
- FDA label
- Download (503 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Diarrhoea Predominant Irritable Bowel Syndrome 2 3 Completed Treatment Irritable Bowel Syndrome (IBS) 2 3 Enrolling by Invitation Treatment Irritable Bowel Syndrome (IBS) 1 2 Completed Treatment Irritable Bowel Syndrome (IBS) 1 2 Recruiting Treatment Irritable Bowel Syndrome (IBS) 1 2 Withdrawn Treatment Accidental Bowel Leakage / Diarrhea / Fecal Incontinence / Urinary Urge Incontinence 1 2, 3 Withdrawn Treatment Diabetes / Diabetic diarrhea / Diarrhea 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 100 MG Tablet, film coated Oral 75 MG Tablet Oral 100 mg Tablet Oral 75 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 75 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9115091 No 2015-08-25 2028-07-07 US US9205076 No 2015-12-08 2025-03-14 US US8691860 No 2014-04-08 2028-07-07 US US8344011 No 2013-01-01 2025-03-14 US US8609709 No 2013-12-17 2025-03-14 US US7741356 No 2010-06-22 2028-03-25 US US7786158 No 2010-08-31 2025-03-14 US US9364489 No 2016-06-14 2028-07-07 US US8772325 No 2014-07-08 2025-03-14 US US9675587 No 2017-06-13 2033-03-14 US US9700542 No 2017-07-11 2025-03-14 US US9789125 No 2017-10-17 2028-07-07 US US10188632 No 2019-01-29 2033-03-14 US US10213415 No 2019-02-26 2025-03-14 US US11007179 No 2021-05-18 2033-03-14 US US11090291 No 2021-08-17 2033-03-14 US US11160792 No 2021-11-02 2033-03-14 US US11229627 No 2013-03-14 2033-03-14 US US11311516 No 2013-03-14 2033-03-14 US US11484527 No 2013-03-14 2033-03-14 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00268 mg/mL ALOGPS logP 1.08 ALOGPS logP 1.8 Chemaxon logS -5.3 ALOGPS pKa (Strongest Acidic) 3.66 Chemaxon pKa (Strongest Basic) 7.99 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 164.63 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 160.38 m3·mol-1 Chemaxon Polarizability 61.86 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key 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
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA: Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014 Dec 1;92(3):448-56. doi: 10.1016/j.bcp.2014.09.015. Epub 2014 Sep 28. [Article]
- Dove LS, Lembo A, Randall CW, Fogel R, Andrae D, Davenport JM, McIntyre G, Almenoff JS, Covington PS: Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study. Gastroenterology. 2013 Aug;145(2):329-38.e1. doi: 10.1053/j.gastro.2013.04.006. Epub 2013 Apr 9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
References
- Fujita W, Gomes I, Dove LS, Prohaska D, McIntyre G, Devi LA: Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers. Biochem Pharmacol. 2014 Dec 1;92(3):448-56. doi: 10.1016/j.bcp.2014.09.015. Epub 2014 Sep 28. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Organic anion transmembrane transporter activity
- Specific Function
- Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- Canalicular multispecific organic anion transporter 1
- Molecular Weight
- 174205.64 Da
References
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
References
- Davenport JM, Covington P, Bonifacio L, McIntyre G, Venitz J: Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline. J Clin Pharmacol. 2015 May;55(5):534-42. doi: 10.1002/jcph.442. Epub 2015 Jan 14. [Article]
Drug created at October 28, 2015 19:50 / Updated at October 03, 2023 16:58