Alvimopan
Explore a selection of our essential drug information below, or:
Overview
- Description
- A medication used to help the stomach and intestines heal after surgical procedures that involve removing parts of the bowel.
- Description
- A medication used to help the stomach and intestines heal after surgical procedures that involve removing parts of the bowel.
- DrugBank ID
- DB06274
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 0
- Phase 2
- 8
- Phase 3
- 11
- Phase 4
- 5
- Mechanism of Action
- Mu-type opioid receptorAntagonist
- Mu-type opioid receptor
Identification
- Summary
Alvimopan is an opioid antagonist used to reduce healing time of the upper and lower gastrointestinal tract following surgical procedures that involve bowel resection with primary anastomosis.
- Brand Names
- Entereg
- Generic Name
- Alvimopan
- DrugBank Accession Number
- DB06274
- Background
Alvimopan is a peripherally acting μ opioid antagonist. It is used to avoid postoperative ileus following small or large bowel resection and accelerates the gastrointestinal recovery period.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 424.5326
Monoisotopic: 424.236207522 - Chemical Formula
- C25H32N2O4
- Synonyms
- Alvimopan
- Alvimopan anhydrous
- Anhydrous alvimopan
Pharmacology
- Indication
Used to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. Also investigated for use in the treatment of pain (acute or chronic).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Therapies
- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Not Available
- Mechanism of action
Alvimopan competitively binds to mu-opioid receptor in the gastrointestinal tract but, unlike methylnaltrexone which relies upon it ionic charge, alvimopan owes its selectivity for peripheral receptors to its pharmacokinetics. Alvimopan binds to peripheral mu-receptors with a Ki of 0.2 ng/mL.
Target Actions Organism AMu-type opioid receptor antagonistHumans UKappa-type opioid receptor antagonistHumans UDelta-type opioid receptor antagonistHumans - Absorption
Alvimopan's high affinity for the peripheral mu-receptor leads to slower absorption dependent on dissociation from the receptor and subsequently low oral bioavailability of less than 7%.
- Volume of distribution
- 30±10 L
- Protein binding
80% to 90% bound in after entering systemic circulation.
- Metabolism
Alvimopan is primarily metabolized by intestinal flora to an active metabolite although it has no clinically significant contribution to the effects of the drug.
- Route of elimination
Biliary secretion was considered the primary pathway for alvimopan elimination. Unabsorbed drug and unchanged alvimopan resulting from biliary excretion were then hydrolyzed to its ‘metabolite’ by gut microflora. Feces (via biliary excretion) & urine (35%)
- Half-life
10 to 17 hours (gut metabolite: 10 to 18 hours)
- Clearance
- 402 ± 89 mL/min
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
Pathway Category Alvimopan Action Pathway Drug action - 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 softwareAlfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Alvimopan. Benzhydrocodone The risk or severity of adverse effects can be increased when Benzhydrocodone is combined with Alvimopan. Buprenorphine The risk or severity of adverse effects can be increased when Buprenorphine is combined with Alvimopan. Butorphanol The risk or severity of adverse effects can be increased when Butorphanol is combined with Alvimopan. Codeine The risk or severity of adverse effects can be increased when Codeine is combined with Alvimopan. - Food Interactions
- Take with or without food. High-fat meals may reduce the Cmax and AUC by 38% and 21%, respectively; however, the clinical significance of this is unknown.
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.
- Product Ingredients
Ingredient UNII CAS InChI Key Alvimopan dihydrate 677C126AET 170098-38-1 USPVLEIQIUNQGE-DBFLIVQGSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Entereg Capsule 12 mg/1 Oral Merck Sharp & Dohme B.V. 2012-04-16 Not applicable US Entereg Capsule 12 mg/1 Oral Adolor Corporation 2008-05-20 2014-11-30 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alvimopan Capsule 12 mg/1 Oral ENDO USA, Inc. 2023-05-03 Not applicable US Alvimopan Capsule 12 mg/1 Oral Golden State Medical Supply, Inc. 2023-08-31 Not applicable US Alvimopan Capsule 12 mg/1 Oral Actavis Pharma, Inc. 2020-12-01 Not applicable US Alvimopan Capsule 12 mg/1 Oral Hikma Pharmaceuticals USA Inc. 2024-02-06 Not applicable US
Categories
- ATC Codes
- A06AH02 — Alvimopan
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Peptidomimetics
- Sub Class
- Hybrid peptides
- Direct Parent
- Hybrid peptides
- Alternative Parents
- N-acyl-alpha amino acids / Phenylpiperidines / Beta amino acids and derivatives / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Aralkylamines / Fatty amides / Benzene and substituted derivatives / Trialkylamines / Secondary carboxylic acid amides show 8 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid show 26 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q153V49P3Z
- CAS number
- 156053-89-3
- InChI Key
- UPNUIXSCZBYVBB-JVFUWBCBSA-N
- InChI
- InChI=1S/C25H32N2O4/c1-18-16-27(12-11-25(18,2)21-9-6-10-22(28)14-21)17-20(24(31)26-15-23(29)30)13-19-7-4-3-5-8-19/h3-10,14,18,20,28H,11-13,15-17H2,1-2H3,(H,26,31)(H,29,30)/t18-,20-,25+/m0/s1
- IUPAC Name
- 2-[(2S)-2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanamido]acetic acid
- SMILES
- C[C@H]1CN(C[C@H](CC2=CC=CC=C2)C(=O)NCC(O)=O)CC[C@@]1(C)C1=CC(O)=CC=C1
References
- General References
- Wang S, Shah N, Philip J, Caraccio T, Feuerman M, Malone B: Role of alvimopan (entereg) in gastrointestinal recovery and hospital length of stay after bowel resection. P T. 2012 Sep;37(9):518-25. [Article]
- Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R: Clinical trial: alvimopan for the management of post-operative ileus after abdominal surgery: results of an international randomized, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Aug 1;28(3):312-25. [Article]
- Link [Link]
- FDA Approved Drug Products: Entereg (alvimopan) capsules for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0015631
- KEGG Drug
- D02878
- PubChem Compound
- 5488548
- PubChem Substance
- 99443242
- ChemSpider
- 4589864
- BindingDB
- 50088381
- 480639
- ChEBI
- 135686
- ChEMBL
- CHEMBL270190
- ZINC
- ZINC000003802417
- Therapeutic Targets Database
- DAP001140
- PharmGKB
- PA164754864
- PDBe Ligand
- NG0
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Alvimopan
- PDB Entries
- 7ul4
- FDA label
- Download (149 KB)
- MSDS
- Download (127 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Ileus 1 somestatus stop reason just information to hide Not Available Completed Treatment Ileus 1 somestatus stop reason just information to hide Not Available Completed Treatment Ileus / Spine Fusion 1 somestatus stop reason just information to hide Not Available Terminated Treatment Ventral Hernias 1 somestatus stop reason just information to hide 4 Completed Treatment Constipation 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Adolor Corp.
- GlaxoSmithKline Inc.
- Pharmaceutics International Inc.
- Dosage Forms
Form Route Strength Capsule Oral 12 mg/1 - Prices
Unit description Cost Unit Entereg 12 mg capsule 79.5USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5250542 No 1993-10-05 2016-03-29 US US6469030 No 2002-10-22 2020-11-29 US US8645160 No 2014-02-04 2029-06-18 US US8112290 No 2012-02-07 2030-07-31 US US8946262 No 2015-02-03 2030-02-12 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <0.1 mg/mL FDA Label - Predicted Properties
Property Value Source Water Solubility 0.00834 mg/mL ALOGPS logP 3.25 ALOGPS logP 0.82 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 3.71 Chemaxon pKa (Strongest Basic) 10.66 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 89.87 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 120.56 m3·mol-1 Chemaxon Polarizability 46.77 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9103 Blood Brain Barrier - 0.96 Caco-2 permeable - 0.6875 P-glycoprotein substrate Substrate 0.8627 P-glycoprotein inhibitor I Non-inhibitor 0.6845 P-glycoprotein inhibitor II Non-inhibitor 0.6478 Renal organic cation transporter Non-inhibitor 0.8596 CYP450 2C9 substrate Non-substrate 0.7966 CYP450 2D6 substrate Non-substrate 0.7292 CYP450 3A4 substrate Substrate 0.5908 CYP450 1A2 substrate Non-inhibitor 0.9362 CYP450 2C9 inhibitor Non-inhibitor 0.9109 CYP450 2D6 inhibitor Non-inhibitor 0.7964 CYP450 2C19 inhibitor Non-inhibitor 0.8729 CYP450 3A4 inhibitor Non-inhibitor 0.8447 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9803 Ames test Non AMES toxic 0.8684 Carcinogenicity Non-carcinogens 0.8594 Biodegradation Not ready biodegradable 0.9694 Rat acute toxicity 2.6978 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9599 hERG inhibition (predictor II) Non-inhibitor 0.7208
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0fr6-5947300000-a56d3fba4a79398cd53e Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0219300000-d56ff642d624ca5fc91a Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-0029000000-f5a1474573c092bf0be4 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-05di-0139500000-524d13b83a6662aa1891 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0zgi-4039000000-fae385831c550a775830 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0932000000-44b2574581618c073546 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0159-3984000000-76ee8c5c81d779cd5486 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 216.9819581 predictedDarkChem Lite v0.1.0 [M-H]- 190.7723 predictedDeepCCS 1.0 (2019) [M+H]+ 215.1965581 predictedDarkChem Lite v0.1.0 [M+H]+ 193.16786 predictedDeepCCS 1.0 (2019) [M+Na]+ 215.0059581 predictedDarkChem Lite v0.1.0 [M+Na]+ 199.3567 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity)
- Specific Function
- beta-endorphin receptor activity
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Kraft MD: Emerging pharmacologic options for treating postoperative ileus. Am J Health Syst Pharm. 2007 Oct 15;64(20 Suppl 13):S13-20. [Article]
- Buchler MW, Seiler CM, Monson JR, Flamant Y, Thompson-Fawcett MW, Byrne MM, Mortensen ER, Altman JF, Williamson R: Clinical trial: alvimopan for the management of post-operative ileus after abdominal surgery: results of an international randomized, double-blind, multicentre, placebo-controlled clinical study. Aliment Pharmacol Ther. 2008 Aug 1;28(3):312-25. [Article]
- Saufl NM, Strzyzewski N: Nurses are everywhere: a practical perspective on the surgical team in managing postoperative ileus. J Perianesth Nurs. 2006 Apr;21(2A Suppl):S24-9. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [Article]
- Schmidt WK: Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist. Am J Surg. 2001 Nov;182(5A Suppl):27S-38S. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- G-protein coupled opioid receptor that functions as a receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as a receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions
- Specific Function
- dynorphin receptor activity
- Gene Name
- OPRK1
- Uniprot ID
- P41145
- Uniprot Name
- Kappa-type opioid receptor
- Molecular Weight
- 42644.665 Da
References
- Beattie DT, Cheruvu M, Mai N, O'Keefe M, Johnson-Rabidoux S, Peterson C, Kaufman E, Vickery R: The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone. Naunyn Schmiedebergs Arch Pharmacol. 2007 May;375(3):205-20. Epub 2007 Mar 6. [Article]
- Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine
- Specific Function
- G protein-coupled enkephalin receptor activity
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
References
- Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [Article]
- Beattie DT, Cheruvu M, Mai N, O'Keefe M, Johnson-Rabidoux S, Peterson C, Kaufman E, Vickery R: The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone. Naunyn Schmiedebergs Arch Pharmacol. 2007 May;375(3):205-20. Epub 2007 Mar 6. [Article]
Drug created at March 19, 2008 16:20 / Updated at February 21, 2021 18:52