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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H32N2O4.H2O
Molecular Weight 442.5479
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALVIMOPAN MONOHYDRATE

SMILES

O.C[C@H]1CN(C[C@H](CC2=CC=CC=C2)C(=O)NCC(O)=O)CC[C@@]1(C)C3=CC=CC(O)=C3

InChI

InChIKey=XSTFUWQLHMJPFG-NABRLNOVSA-N
InChI=1S/C25H32N2O4.H2O/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);1H2/t18-,20-,25+;/m0./s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C25H32N2O4
Molecular Weight 424.5326
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8057274 | http://adisinsight.springer.com/drugs/800003539

Alvimopan (LY246736, ADL 8-2698, trade name Entereg) is a potent, peripherally selective mu-opioid receptor antagonist. Alvimopan was developed by Adolor Corporation (now Cubist Pharmaceuticals) and GlaxoSmithKline for the treatment of postoperative ileus. Postoperative ileus is the impairment of gastrointestinal motility after intra-abdominal surgery or other non-abdominal surgeries. This may potentially delay gastrointestinal recovery and hospital discharge until its resolution. Morphine and other mu-opioid receptor agonists are universally used for the treatment of acute postsurgical pain; however, they are known to have an inhibitory effect on gastrointestinal motility and may prolong the duration of postoperative ileus. Following oral administration, alvimopan antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion by competitively binding to gastrointestinal tract mu-opioid receptors.

Originator

Curator's Comment: # Eli Lilly

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.77 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
ENTEREG

Approved Use

ENTEREG is a peripherally acting μ-opioid receptor antagonist indicated to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis.

Launch Date

2008
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
10.98 ng/mL
12 mg 2 times / day multiple, oral
dose: 12 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ALVIMOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
40.2 ng × h/mL
12 mg 2 times / day multiple, oral
dose: 12 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ALVIMOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.5 h
12 mg 2 times / day multiple, oral
dose: 12 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ALVIMOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
20%
12 mg 2 times / day multiple, oral
dose: 12 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ALVIMOPAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
120 mg single, oral
Highest studied dose
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, adult
48 mg 1 times / day multiple, oral
Highest studied dose
Dose: 48 mg, 1 times / day
Route: oral
Route: multiple
Dose: 48 mg, 1 times / day
Sources:
healthy, adult
12 mg 2 times / day multiple, oral
Recommended
Dose: 12 mg, 2 times / day
Route: oral
Route: multiple
Dose: 12 mg, 2 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Other AEs: Ascites, Ileus...
Other AEs:
Ascites (serious, 1 patient)
Ileus (serious, 1 patient)
Electrolyte imbalance (serious, 1 patient)
Failure to thrive (serious, 1 patient)
Syncope (serious, 1 patient)
Wound infection (serious, 2 patients)
Wound complication (serious, 1 patient)
Mania (serious, 1 patient)
Hypertension (below serious, 3 patients)
Constipation (below serious, 18 patients)
Diarrhea (below serious, 6 patients)
Dyspepsia (below serious, 1 patient)
Nausea (below serious, 20 patients)
Vomiting (below serious, 9 patients)
Anorexia (below serious, 4 patients)
Esophagitis (below serious, 1 patient)
Gastroparesis (below serious, 1 patient)
Weight loss (below serious, 3 patients)
Leukocytosis (below serious, 4 patients)
International normalized ratio increased (below serious, 1 patient)
Electrolyte imbalance (below serious, 8 patients)
Hypomagnesemia (below serious, 2 patients)
Elevated liver enzymes (below serious, 2 patients)
Delirium (below serious, 3 patients)
Insomnia (below serious, 1 patient)
Sensory neuropathy (below serious, 3 patients)
Cystostomy (below serious, 1 patient)
Pelvic abscess (below serious, 1 patient)
Urinary tract obstruction (below serious, 1 patient)
Allergic reaction to chemotherapy (below serious, 1 patient)
Pneumonitis (below serious, 2 patients)
Pneumothorax (below serious, 2 patients)
Wound infection (below serious, 7 patients)
Skin infection (below serious, 2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Allergic reaction to chemotherapy below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Cystostomy below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Dyspepsia below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Esophagitis below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Gastroparesis below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Insomnia below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
International normalized ratio increased below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Pelvic abscess below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Urinary tract obstruction below serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Constipation below serious, 18 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Elevated liver enzymes below serious, 2 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Hypomagnesemia below serious, 2 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Pneumonitis below serious, 2 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Pneumothorax below serious, 2 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Skin infection below serious, 2 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Nausea below serious, 20 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Delirium below serious, 3 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Hypertension below serious, 3 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Sensory neuropathy below serious, 3 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Weight loss below serious, 3 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Anorexia below serious, 4 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Leukocytosis below serious, 4 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Diarrhea below serious, 6 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Wound infection below serious, 7 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Electrolyte imbalance below serious, 8 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Vomiting below serious, 9 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Ascites serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Electrolyte imbalance serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Failure to thrive serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Ileus serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Mania serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Syncope serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Wound complication serious, 1 patient
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
Wound infection serious, 2 patients
12 mg 2 times / day steady, oral
Dose: 12 mg, 2 times / day
Route: oral
Route: steady
Dose: 12 mg, 2 times / day
Sources:
unhealthy
n = 66
Health Status: unhealthy
Condition: ovarian cancer
Population Size: 66
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no
no
no
no
no
no
no (co-administration study)
Comment: based on study using MDCKII cells, digoxin transport not affected
Page: 66, 67
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Selective postoperative inhibition of gastrointestinal opioid receptors.
2001 Sep 27
Awakening the sleeping postsurgical abdomen.
2002 Apr
Opioid-induced bowel dysfunction: pathophysiology and potential new therapies.
2003
Methylnaltrexone and alvimopan: economic management of opioid-induced bowel dysfunction.
2004 Apr
Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans.
2004 May 6
Preclinical studies of opioids and opioid antagonists on gastrointestinal function.
2004 Oct
Molecule of the month. Alvimopan hydrate.
2005 Jun
Alvimopan: an oral, peripherally acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction--a 21-day treatment-randomized clinical trial.
2005 Mar
Alvimopan for the management of postoperative ileus.
2005 Sep
Peripheral opioids for functional GI disease: a reappraisal.
2006
A double-blind, randomized, placebo-controlled phase III study of the safety of alvimopan in patients who undergo simple total abdominal hysterectomy.
2006 Aug
Pain management research goes beyond the obvious.
2006 Dec 1
Postoperative upper and lower gastrointestinal recovery and gastrointestinal morbidity in patients undergoing bowel resection: pooled analysis of placebo data from 3 randomized controlled trials.
2006 Mar
Postoperative ileus-related morbidity profile in patients treated with alvimopan after bowel resection.
2007 Apr
Treatment of opioid-induced gut dysfunction.
2007 Feb
Cancer-related constipation.
2007 Jul
Emerging pharmacologic options for treating postoperative ileus.
2007 Oct 15
Alvimopan: a peripherally acting mu-opioid receptor antagonist.
2007 Sep
New approaches to the treatment of opioid-induced constipation.
2008 Aug
Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults.
2008 Jan 23
Alvimopan hastens recovery from abdominal surgery.
2008 Jul
Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles.
2008 Mar 15
Management of postoperative ileus: focus on alvimopan.
2008 Oct
New drugs: methylnaltrexone bromide, alvimopan, and rilonacept.
2008 Sep-Oct
Pharmacological management of postoperative ileus.
2009 Apr
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus.
2009 Apr 4
Alvimopan for postoperative ileus: only one piece of the puzzle.
2009 Jul 15
Preventing paralytic ileus: can the anesthesiologist help.
2009 Jun
Peripherally acting mu-opioid receptor antagonists and postoperative ileus: mechanisms of action and clinical applicability.
2009 Jun
New drugs 09, part 1.
2009 Oct-Dec
Alvimopan (entereg) for the management of postoperative ileus in patients undergoing bowel resection.
2010 Jan
The effects of a short course of antibiotics on alvimopan and metabolite pharmacokinetics.
2010 Mar
Patents

Sample Use Guides

12 mg administered 30 minutes to 5 hours prior to surgery followed by 12 mg twice daily for up to 7 days for a maximum of 15 doses
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: In morphine-naive guinea pig ileum alvimopan increased, the amplitude of electrically evoked contractions and spontaneous mechanical activity.
Unknown
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:30:16 GMT 2023
Edited
by admin
on Sat Dec 16 01:30:16 GMT 2023
Record UNII
28LAR2REDG
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALVIMOPAN MONOHYDRATE
Common Name English
(((2S)-2-(((3R,4R)-4-(3-HYDROXYPHENYL)-3,4-DIMETHYLPIPERIDIN-1-YL)METHYL)-3-PHENYLPROPANOYL)AMINO)ACETIC ACID MONOHYDRATE
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID30160641
Created by admin on Sat Dec 16 01:30:17 GMT 2023 , Edited by admin on Sat Dec 16 01:30:17 GMT 2023
PRIMARY
PUBCHEM
71587995
Created by admin on Sat Dec 16 01:30:17 GMT 2023 , Edited by admin on Sat Dec 16 01:30:17 GMT 2023
PRIMARY
CAS
1383577-62-5
Created by admin on Sat Dec 16 01:30:17 GMT 2023 , Edited by admin on Sat Dec 16 01:30:17 GMT 2023
PRIMARY
FDA UNII
28LAR2REDG
Created by admin on Sat Dec 16 01:30:17 GMT 2023 , Edited by admin on Sat Dec 16 01:30:17 GMT 2023
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY