ALVIMOPAN ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H32N2O4
Molecular Weight	424.5326
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=UPNUIXSCZBYVBB-JVFUWBCBSA-N

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

HIDE SMILES / InChI

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8057274	Antagonist 2760		0.77 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postoperative ileus 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	Preventing		Approved 8360	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 1.21124159E12

C_max

Value	Dose	Co-administered	Analyte	Population
10.98 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	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

Value	Dose	Co-administered	Analyte	Population
40.2 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
20% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	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

Dose	Population	Adverse events
120 mg single, oral Highest studied dose Dose: 120 mg Route: oral Route: single Dose: 120 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	healthy, adult Health Status: healthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021775lbl.pdf
12 mg 2 times / day steady, oral Dose: 12 mg, 2 times / day Route: oral Route: steady Dose: 12 mg, 2 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01704651	unhealthy n = 66 Health Status: unhealthy Condition: ovarian cancer Population Size: 66 Sources: https://clinicaltrials.gov/ct2/show/NCT01704651	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: https://clinicaltrials.gov/ct2/show/NCT01704651

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579	inhibitor 1752 inducer 383	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2A6 704 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP2E1 876 P-gp 1437	CYP 266 P-gp 1527	CYP1A2 689 CYP2B6 538 CYP2C19 290 CYP3A4/5 120

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 95.0	no [IC50 >50 uM]
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 32, 34, 35, 95	no
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 32, 34, 35	no
CYP2C19 1537	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 32, 34, 35	no
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 32, 34, 35	no
CYP3A4/5 330	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 32, 34, 35, 94	no
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 66, 67	no	no (co-administration study) Comment: based on study using MDCKII cells, digoxin transport not affected Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 66, 67

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 266	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 94.0	no
P-gp 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_BIOPHARMR.pdf Page: 67, 97	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/021775_ENTEREG_CAPSULES_PHARMR.pdf Page: 99, 108

PubMed

Title	Date	PubMed
		18373729
Methylnaltrexone and alvimopan: economic management of opioid-induced bowel dysfunction.	2004 Apr	19807518
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus.	2007	17844725
Patterns of gastrointestinal recovery after bowel resection and total abdominal hysterectomy: pooled results from the placebo arms of alvimopan phase III North American clinical trials.	2007 Jul	17617331
Cancer-related constipation.	2007 Jul	17588352
Moving ahead or falling behind?	2007 Jun	17541443
Peripherally acting opioid antagonists in the treatment of opiate-related constipation: a systematic review.	2007 Nov	17900855
Alvimopan accelerates gastrointestinal recovery after bowel resection regardless of age, gender, race, or concomitant medication use.	2007 Oct	17950339
Alvimopan: a peripherally acting mu-opioid receptor antagonist.	2007 Sep	17940638
Is alvimopan a safe and effective treatment for postoperative ileus?	2007 Sep	17646856
Alvimopan.	2008	18778122
Opioid-induced constipation in intensive care patients: relief in sight?	2008	18598388
Mu-opioid antagonists for opioid-induced bowel dysfunction.	2008 Apr 16	18425947
New approaches to the treatment of opioid-induced constipation.	2008 Aug	18924451
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.	2008 Aug 1	19086236
Alvimopan (Entereg) for postoperative ileus.	2008 Dec 1	19037186
Alvimopan hastens recovery from abdominal surgery.	2008 Jul	18757026
New drug to restore bowel function approved under new FDA rules.	2008 Jul 1	18574004
Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain.	2008 Jul 15	18164818
Alvimopan and COX-2 inhibition reverse opioid and inflammatory components of postoperative ileus.	2008 Jun	18266613
Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles.	2008 Mar 15	18313920
Pharmacokinetics of alvimopan and its metabolite in healthy volunteers and patients in postoperative ileus trials.	2008 May	17653140
Gastrointestinal tract recovery in patients undergoing bowel resection: results of a randomized trial of alvimopan and placebo with a standardized accelerated postoperative care pathway.	2008 Nov	19015469
Alvimopan (Entereg), a Peripherally Acting mu-Opioid Receptor Antagonist For Postoperative Ileus.	2008 Oct	19750041
Management of postoperative ileus: focus on alvimopan.	2008 Oct	19209278
Postoperative ileus: strategies for reduction.	2008 Oct	19209273
Development of peripheral opioid antagonists' new insights into opioid effects.	2008 Oct	18828971
Alvimopan.	2008 Sep	19172688
Efficacy and safety of mu-opioid antagonists in the treatment of opioid-induced bowel dysfunction: systematic review and meta-analysis of randomized controlled trials.	2008 Sep	18828197
[News from the cochrane library: mu opioid antagonists for opioid-induced bowel dysfunction].	2008 Sep	18810678
Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus.	2008 Sep	18694369
New drugs: methylnaltrexone bromide, alvimopan, and rilonacept.	2008 Sep-Oct	18826910
Pharmacological management of postoperative ileus.	2009 Apr	19399212
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus.	2009 Apr 4	19217656
Economic analysis of alvimopan in North American Phase III efficacy trials.	2009 Aug 1	19635772
Peripheral opioid antagonism.	2009 Dec	20092510
Pathogenesis and management of postoperative ileus.	2009 Feb	20119556
Alvimopan for postoperative ileus: only one piece of the puzzle.	2009 Jul 15	19574607
Alvimopan for postoperative ileus.	2009 Jul 15	19574601
Preventing paralytic ileus: can the anesthesiologist help.	2009 Jun	19583062
Peripherally acting mu-opioid receptor antagonists and postoperative ileus: mechanisms of action and clinical applicability.	2009 Jun	19448206
Opioid receptors in the gastrointestinal tract.	2009 Jun 5	19345246
An overview of constipation and newer therapies.	2009 Jun-Jul	19531698
New drugs 09, part 1.	2009 Oct-Dec	20029303
Comment on alvimopan guidelines.	2009 Sep	19687658
Pharmacologic options to prevent postoperative ileus.	2009 Sep	19602600
Intensive Care Unit-acquired infection as a side effect of sedation.	2010	20226064
Alvimopan (entereg) for the management of postoperative ileus in patients undergoing bowel resection.	2010 Jan	20182561
The effects of a short course of antibiotics on alvimopan and metabolite pharmacokinetics.	2010 Mar	19797535
Gastrointestinal recovery after laparoscopic colectomy: results of a prospective, observational, multicenter study.	2010 Mar	19688390

Patents

Sample Use Guides

In Vivo Use Guide

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

Unknown

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:46:38 UTC 2023` Edited by `admin` on `Wed Jul 05 23:46:38 UTC 2023`
Record UNII	Q153V49P3Z
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ALVIMOPAN ANHYDROUS

Common Name

English

Alvimopan [WHO-DD]

Common Name

English

ALVIMOPAN [MI]

Common Name

English

N-((2S)-2-(((3R,4R)-4-(3-HYDROXYPHENYL)-3,4-DIMETHYL-1-PIPERIDINYL)METHYL)-1-OXO-3-PHENYLPROPYL)GLYCINE

Systematic Name

English

ANHYDROUS ALVIMOPAN

Common Name

English

ALVIMOPAN [MART.]

Common Name

English

GLYCINE, N-(2-((4-(3-HYDROXYPHENYL)-3,4-DIMETHYL-1-PIPERIDINYL)METHYL)-1-OXO-3-PHENYLPROPYL)-, (3R-((S*),3.ALPHA.,4.ALPHA.))-

Common Name

English

alvimopan [INN]

Common Name

English

ANHYDROUS ALVIMOPAN [MART.]

Common Name

English

((2(S)-((4(R)-(3-HYDROXYPHENYL)-3(R),4-DIMETHYL-1-PIPERIDINYL)METHYL)-1-OXO-3-PHENYLPROPYL)AMINO)ACETIC ACID

Systematic Name

English

(((2S)-2-(((3R,4R)-4-(3-HYDROXYPHENYL)-3,4-DIMETHYLPIPERIDIN-1-YL)METHYL)-3-PHENYLPROPANOYL)AMINO)ACETIC ACID

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000000154