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Identification
NameAlvimopan
Accession NumberDB06274
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
Synonyms
Alvimopan anhydrous
Anhydrous alvimopan
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Enteregcapsule12 mg/1oralMerck Sharp & Dohme Corp.2012-04-16Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Alvimopan dihydrate
170098-38-1
Thumb
  • InChI Key: USPVLEIQIUNQGE-DBFLIVQGSA-N
  • Monoisotopic Mass: 460.257336887
  • Average Mass: 460.571
DBSALT001865
Categories
UNIIQ153V49P3Z
CAS number156053-89-3
WeightAverage: 424.5326
Monoisotopic: 424.236207522
Chemical FormulaC25H32N2O4
InChI KeyInChIKey=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[[email protected]]1CN(C[[email protected]](CC2=CC=CC=C2)C(=O)NCC(O)=O)CC[C@@]1(C)C1=CC(O)=CC=C1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentHybrid peptides
Alternative Parents
Substituents
  • Hybrid peptide
  • N-acyl-aliphatic-alpha amino acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Phenylpiperidine
  • Beta amino acid or derivatives
  • Phenylpropylamine
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Aralkylamine
  • Phenol
  • Fatty acyl
  • Benzenoid
  • Piperidine
  • Fatty amide
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed 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).
PharmacodynamicsNot Available
Mechanism of actionAlvimopan competitively binds to mu-opioid receptor in the gastrointestinal tract. Unlike methylnaltrexone (another peripherally acting mu-receptor antagonist) that bears a quaternary amine, alvimopan owes its selectivity for peripheral receptors to its kinetics. Alvimopan binds to peripheral mu-receptors with a Ki of 0.2 ng/mL and dissociates slower than most other ligands.
Related Articles
AbsorptionAlvimopan's high affinity for the peripheral mu-receptor results in an absolute oral bioavailability of less than 7%.
Volume of distribution
  • 30±10 L
Protein binding80% to 90% of systemically available alvimopan is bound to plasma protein.
Metabolism

Alvimopan undergoes no significant hepatic metabolism, but is metabolized by intestinal flora. Gut metabolism produces an active metabolite with no clinically significant contribution to drug effect.

Route of eliminationBiliary 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 life10 to 17 hours (gut metabolite: 10 to 18 hours)
Clearance
  • 402 ± 89 mL/min
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Alvimopan Action PathwayDrug actionSMP00685
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
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)
US5250542 No1996-03-292016-03-29Us
US6469030 No2000-11-292020-11-29Us
US8112290 No2010-07-312030-07-31Us
US8645160 No2009-06-182029-06-18Us
US8946262 No2010-02-122030-02-12Us
Properties
StateSolid
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
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. [PubMed:23066346 ]
  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. [PubMed:19086236 ]
  3. Link [Link]
External Links
ATC CodesA06AH02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (149 KB)
MSDSDownload (127 KB)
Interactions
Drug Interactions
Drug
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil 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.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Alvimopan.
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Alvimopan.
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Alvimopan.
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Alvimopan.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Alvimopan.
MethylnaltrexoneThe risk or severity of adverse effects can be increased when Methylnaltrexone is combined with Alvimopan.
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Alvimopan.
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Alvimopan.
NaloxegolThe risk or severity of adverse effects can be increased when Alvimopan is combined with Naloxegol.
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Alvimopan.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Alvimopan.
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Alvimopan.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Alvimopan.
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Alvimopan.
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Alvimopan.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Alvimopan.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Alvimopan.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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. 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 dissociati...
Gene Name:
OPRM1
Uniprot ID:
P35372
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. [PubMed:17909271 ]
  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. [PubMed:19086236 ]
  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. [PubMed:16597533 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  5. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [PubMed:15882122 ]
  6. Schmidt WK: Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist. Am J Surg. 2001 Nov;182(5A Suppl):27S-38S. [PubMed:11755894 ]
Kind
Protein
Organism
Human
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 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 th...
Gene Name:
OPRK1
Uniprot ID:
P41145
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. [PubMed:17340127 ]
  2. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [PubMed:15882122 ]
Kind
Protein
Organism
Human
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 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 neurot...
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [PubMed:15882122 ]
  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. [PubMed:17340127 ]
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Drug created on March 19, 2008 10:20 / Updated on August 24, 2016 01:52