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Trials

Economics

Properties

Spectra

Taxonomy

Alvimopan

Targets (3)Biointeractions (3)

Identification

Name

Alvimopan

Accession Number

DB06274

Type

Small Molecule

Groups

Approved, Investigational

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

Similar Structures

Synonyms

Alvimopan
Alvimopan anhydrous
Anhydrous alvimopan

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Alvimopan dihydrate	677C126AET	170098-38-1	USPVLEIQIUNQGE-DBFLIVQGSA-N

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Entereg	Capsule	12 mg/1	Oral	Adolor Corporation	2008-05-20	2014-11-30
Entereg	Capsule	12 mg/1	Oral	Merck Sharp & Dohme Corp.	2012-04-16	Not applicable

Categories

UNII

Q153V49P3Z

CAS number

156053-89-3

Weight

Average: 424.5326
Monoisotopic: 424.236207522

Chemical Formula

C₂₅H₃₂N₂O₄

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

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).

Associated Therapies

To accelerate the time to upper and lower gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis

Pharmacodynamics

Not Available

Mechanism of action

Alvimopan 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.

Target	Actions	Organism
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 results in an absolute oral bioavailability of less than 7%.

Volume of distribution

30±10 L

Protein binding

80% 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 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

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Alvimopan Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
Alfentanil	The risk or severity of adverse effects can be increased when Alfentanil is combined with Alvimopan.
Alphacetylmethadol	The risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Alvimopan.
Alphaprodine	The risk or severity of adverse effects can be increased when Alphaprodine is combined with Alvimopan.
Bezitramide	The risk or severity of adverse effects can be increased when Bezitramide 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.
Carfentanil	The risk or severity of adverse effects can be increased when Carfentanil is combined with Alvimopan.
Codeine	The risk or severity of adverse effects can be increased when Codeine is combined with Alvimopan.
Dextromoramide	The risk or severity of adverse effects can be increased when Dextromoramide is combined with Alvimopan.
Dextropropoxyphene	The risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Alvimopan.

Food Interactions

Not Available

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. [PubMed:23066346]
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]
Link [Link]

External Links

Human Metabolome Database: HMDB0015631
KEGG Drug: D02878
PubChem Compound: 5488548
PubChem Substance: 99443242
ChemSpider: 4589864
BindingDB: 50088381
ChEBI: 135686
ChEMBL: CHEMBL270190
Therapeutic Targets Database: DAP001140
PharmGKB: PA164754864
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Alvimopan

ATC Codes

A06AH02 — Alvimopan

FDA label

Download (149 KB)

MSDS

Download (127 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Completed	Treatment	Bowel Dysfunction / Malignancies	1
2	Completed	Treatment	Bowel Dysfunction / Occasional Constipation	1
2	Completed	Treatment	Laparoscopic Colonic Resection	1
2	Recruiting	Treatment	Ileus	1
2	Terminated	Treatment	Malignancies / Occasional Constipation	1
3	Completed	Prevention	Cancer of the Ovary / Fallopian Tube Cancer / Malignant Peritoneal Neoplasm / Primary Peritoneal Cancer	1
3	Completed	Treatment	Bowel Dysfunction / Occasional Constipation	3
3	Completed	Treatment	Ileus	4
3	Not Yet Recruiting	Treatment	Bladder Cancers	1
3	Not Yet Recruiting	Treatment	Ileus / Surgery, Colorectal	1
4	Completed	Treatment	Postoperative paralytic ileus	1
4	Not Yet Recruiting	Prevention	Post Operative Ileus	1
4	Recruiting	Treatment	Occasional Constipation	1
4	Withdrawn	Treatment	Pain, Acute / Postoperative pain / Surgery, Colorectal	1
Not Available	Active Not Recruiting	Treatment	Fusion of Spine (Disease) / Ileus	1
Not Available	Completed	Not Available	Ileus	1
Not Available	Completed	Treatment	Ileus	1
Not Available	Recruiting	Prevention	Ventral Hernias	1

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)
US5250542	No	1993-10-05	2016-03-29
US6469030	No	2002-10-22	2020-11-29
US8645160	No	2014-02-04	2029-06-18
US8112290	No	2012-02-07	2030-07-31
US8946262	No	2015-02-03	2030-02-12

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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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 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: Hybrid peptide / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid / Phenylpiperidine / Beta amino acid or derivatives / Alpha-amino acid or derivatives / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Aralkylamine
show 26 more
Molecular Framework: Aromatic heteromonocyclic compounds
External Descriptors: Not Available

Targets

Details1. Mu-type opioid receptor

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

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]
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]
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]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [PubMed:15882122]
Schmidt WK: Alvimopan* (ADL 8-2698) is a novel peripheral opioid antagonist. Am J Surg. 2001 Nov;182(5A Suppl):27S-38S. [PubMed:11755894]

Details2. Kappa-type opioid receptor

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

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]
Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [PubMed:15882122]

Details3. Delta-type opioid receptor

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

Neary P, Delaney CP: Alvimopan. Expert Opin Investig Drugs. 2005 Apr;14(4):479-88. [PubMed:15882122]
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]

Drug created on March 19, 2008 10:20 / Updated on December 16, 2018 06:52

Alvimopan

Identification

Structure for Alvimopan (DB06274)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References