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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyAlvimopan
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
Structure for DB06274 (Alvimopan)
- Synonyms
- 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 Merck Sharp & Dohme Limited 2012-04-16 Not applicable US 
- 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
- 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 antagonistHuman UKappa-type opioid receptor antagonistHuman UDelta-type opioid receptor antagonistHuman - 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 Drug group Alfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Alvimopan. Approved, Illicit Alphacetylmethadol The risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Alvimopan. Experimental, Illicit Alphaprodine The risk or severity of adverse effects can be increased when Alphaprodine is combined with Alvimopan. Illicit Bezitramide The risk or severity of adverse effects can be increased when Bezitramide is combined with Alvimopan. Experimental, Illicit, Withdrawn Buprenorphine The risk or severity of adverse effects can be increased when Buprenorphine is combined with Alvimopan. Approved, Illicit, Investigational, Vet Approved Butorphanol The risk or severity of adverse effects can be increased when Butorphanol is combined with Alvimopan. Approved, Illicit, Vet Approved Carfentanil The risk or severity of adverse effects can be increased when Carfentanil is combined with Alvimopan. Illicit, Investigational, Vet Approved Codeine The risk or severity of adverse effects can be increased when Codeine is combined with Alvimopan. Approved, Illicit Dextromoramide The risk or severity of adverse effects can be increased when Dextromoramide is combined with Alvimopan. Experimental, Illicit Dextropropoxyphene The risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Alvimopan. Approved, Illicit, Investigational, Withdrawn Dezocine The risk or severity of adverse effects can be increased when Dezocine is combined with Alvimopan. Approved, Investigational Dihydrocodeine The risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Alvimopan. Approved, Illicit Dihydroetorphine The risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Alvimopan. Experimental, Illicit Dihydromorphine The risk or severity of adverse effects can be increased when Dihydromorphine is combined with Alvimopan. Experimental, Illicit Diphenoxylate The risk or severity of adverse effects can be increased when Diphenoxylate is combined with Alvimopan. Approved, Illicit DPDPE The risk or severity of adverse effects can be increased when DPDPE is combined with Alvimopan. Experimental Ethylmorphine The risk or severity of adverse effects can be increased when Ethylmorphine is combined with Alvimopan. Approved, Illicit Etorphine The risk or severity of adverse effects can be increased when Etorphine is combined with Alvimopan. Illicit, Vet Approved Fentanyl The risk or severity of adverse effects can be increased when Fentanyl is combined with Alvimopan. Approved, Illicit, Investigational, Vet Approved Heroin The risk or severity of adverse effects can be increased when Heroin is combined with Alvimopan. Approved, Illicit, Investigational Hydrocodone The risk or severity of adverse effects can be increased when Hydrocodone is combined with Alvimopan. Approved, Illicit Hydromorphone The risk or severity of adverse effects can be increased when Hydromorphone is combined with Alvimopan. Approved, Illicit Ketobemidone The risk or severity of adverse effects can be increased when Ketobemidone is combined with Alvimopan. Approved, Investigational Levomethadyl Acetate The risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Alvimopan. Approved, Investigational Levorphanol The risk or severity of adverse effects can be increased when Levorphanol is combined with Alvimopan. Approved Lofentanil The risk or severity of adverse effects can be increased when Lofentanil is combined with Alvimopan. Illicit Meptazinol The risk or severity of adverse effects can be increased when Meptazinol is combined with Alvimopan. Experimental Methadone The risk or severity of adverse effects can be increased when Methadone is combined with Alvimopan. Approved Methadyl Acetate The risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Alvimopan. Approved, Illicit Methylnaltrexone The risk or severity of adverse effects can be increased when Alvimopan is combined with Methylnaltrexone. Approved Morphine The risk or severity of adverse effects can be increased when Morphine is combined with Alvimopan. Approved, Investigational Nalbuphine The risk or severity of adverse effects can be increased when Nalbuphine is combined with Alvimopan. Approved Naloxegol The risk or severity of adverse effects can be increased when Alvimopan is combined with Naloxegol. Approved Nicomorphine The risk or severity of adverse effects can be increased when Nicomorphine is combined with Alvimopan. Experimental Normethadone The risk or severity of adverse effects can be increased when Normethadone is combined with Alvimopan. Approved, Illicit Opium The risk or severity of adverse effects can be increased when Opium is combined with Alvimopan. Approved, Illicit Oxycodone The risk or severity of adverse effects can be increased when Oxycodone is combined with Alvimopan. Approved, Illicit, Investigational Oxymorphone The risk or severity of adverse effects can be increased when Oxymorphone is combined with Alvimopan. Approved, Investigational, Vet Approved Pentazocine The risk or severity of adverse effects can be increased when Pentazocine is combined with Alvimopan. Approved, Vet Approved Pethidine The risk or severity of adverse effects can be increased when Pethidine is combined with Alvimopan. Approved Phenazocine The risk or severity of adverse effects can be increased when Phenazocine is combined with Alvimopan. Experimental Phenoperidine The risk or severity of adverse effects can be increased when Phenoperidine is combined with Alvimopan. Experimental Piritramide The risk or severity of adverse effects can be increased when Piritramide is combined with Alvimopan. Approved, Investigational Remifentanil The risk or severity of adverse effects can be increased when Remifentanil is combined with Alvimopan. Approved Sufentanil The risk or severity of adverse effects can be increased when Sufentanil is combined with Alvimopan. Approved, Investigational Tapentadol The risk or severity of adverse effects can be increased when Tapentadol is combined with Alvimopan. Approved Tilidine The risk or severity of adverse effects can be increased when Tilidine is combined with Alvimopan. Experimental Tramadol The risk or severity of adverse effects can be increased when Tramadol is combined with Alvimopan. Approved, Investigational - 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 / Cancers 1 2 Completed Treatment Bowel Dysfunction / Occasional Constipation 1 2 Completed Treatment Laparoscopic Colonic Resection 1 2 Recruiting Treatment Ileus 1 2 Terminated Treatment Cancers / 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 1996-03-29 2016-03-29 US US6469030 No 2000-11-29 2020-11-29 US US8645160 No 2009-06-18 2029-06-18 US US8112290 No 2010-07-31 2030-07-31 US US8946262 No 2010-02-12 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 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
- 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...
- 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]
- 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 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]
- 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 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 June 02, 2018 09:44