Alvimopan

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
Thumb
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).

Pharmacology
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Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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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.

TargetActionsOrganism
AMu-type opioid receptor
antagonist
Humans
UKappa-type opioid receptor
antagonist
Humans
UDelta-type opioid receptor
antagonist
Humans
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
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Toxicity

Not Available

Pathways
PathwayCategory
Alvimopan Action PathwayDrug 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.
DrugInteraction
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Alvimopan.
BenzhydrocodoneThe risk or severity of adverse effects can be increased when Benzhydrocodone is combined with Alvimopan.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Alvimopan.
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Alvimopan.
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Alvimopan.
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Alvimopan.
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Alvimopan.
DiamorphineThe risk or severity of adverse effects can be increased when Diamorphine is combined with Alvimopan.
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Alvimopan.
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Alvimopan.
Interactions
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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

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Product Ingredients
IngredientUNIICASInChI Key
Alvimopan dihydrate677C126AET170098-38-1USPVLEIQIUNQGE-DBFLIVQGSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EnteregCapsule12 mg/1OralMerck Sharp & Dohme Corp.2012-04-16Not applicableUS flag
EnteregCapsule12 mg/1OralAdolor Corporation2008-05-202014-11-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AlvimopanCapsule12 mg/1OralActavis Pharma, Inc.2020-12-01Not applicableUS flag

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
  1. 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]
  2. 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]
  3. Link [Link]
  4. FDA Approved Drug Products: Entereg (alvimopan) capsules for oral use [Link]
Human Metabolome Database
HMDB0015631
KEGG Drug
D02878
PubChem Compound
5488548
PubChem Substance
99443242
ChemSpider
4589864
BindingDB
50088381
RxNav
480639
ChEBI
135686
ChEMBL
CHEMBL270190
ZINC
ZINC000003802417
Therapeutic Targets Database
DAP001140
PharmGKB
PA164754864
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alvimopan
FDA label
Download (149 KB)
MSDS
Download (127 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentConstipation1
4CompletedTreatmentPostoperative paralytic ileus1
4RecruitingTreatmentGastrointestinal Dysfunction / Ileus1
4TerminatedPreventionPost Operative Ileus1
4WithdrawnTreatmentPain, Acute / Postoperative pain / Surgery, Colorectal1
3CompletedPreventionFallopian Tube Cancer / Malignant Peritoneal Neoplasm / Ovarian Cancer1
3CompletedTreatmentBowel Dysfunction / Constipation3
3CompletedTreatmentIleus4
3RecruitingTreatmentCancer, Bladder1
3Unknown StatusTreatmentIleus / Surgery, Colorectal1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Adolor Corp.
  • GlaxoSmithKline Inc.
  • Pharmaceutics International Inc.
Dosage Forms
FormRouteStrength
CapsuleOral12 mg/1
Prices
Unit descriptionCostUnit
Entereg 12 mg capsule79.5USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5250542No1993-10-052016-03-29US flag
US6469030No2002-10-222020-11-29US flag
US8645160No2014-02-042029-06-18US flag
US8112290No2012-02-072030-07-31US flag
US8946262No2015-02-032030-02-12US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility<0.1 mg/mLFDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.00834 mg/mLALOGPS
logP3.25ALOGPS
logP0.82ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)3.71ChemAxon
pKa (Strongest Basic)10.66ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area89.87 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity120.56 m3·mol-1ChemAxon
Polarizability46.77 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9103
Blood Brain Barrier-0.96
Caco-2 permeable-0.6875
P-glycoprotein substrateSubstrate0.8627
P-glycoprotein inhibitor INon-inhibitor0.6845
P-glycoprotein inhibitor IINon-inhibitor0.6478
Renal organic cation transporterNon-inhibitor0.8596
CYP450 2C9 substrateNon-substrate0.7966
CYP450 2D6 substrateNon-substrate0.7292
CYP450 3A4 substrateSubstrate0.5908
CYP450 1A2 substrateNon-inhibitor0.9362
CYP450 2C9 inhibitorNon-inhibitor0.9109
CYP450 2D6 inhibitorNon-inhibitor0.7964
CYP450 2C19 inhibitorNon-inhibitor0.8729
CYP450 3A4 inhibitorNon-inhibitor0.8447
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9803
Ames testNon AMES toxic0.8684
CarcinogenicityNon-carcinogens0.8594
BiodegradationNot ready biodegradable0.9694
Rat acute toxicity2.6978 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9599
hERG inhibition (predictor II)Non-inhibitor0.7208
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

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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
  1. Kraft MD: Emerging pharmacologic options for treating postoperative ileus. Am J Health Syst Pharm. 2007 Oct 15;64(20 Suppl 13):S13-20. [Article]
  2. 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]
  3. 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]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  5. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [Article]
  6. Schmidt WK: Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist. Am J Surg. 2001 Nov;182(5A Suppl):27S-38S. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
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
References
  1. 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]
  2. 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
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
  1. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [Article]
  2. 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 on March 19, 2008 16:20 / Updated on February 21, 2021 18:52