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

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

Description

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	Antagonist 2,778		0.77 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Postoperative ileus 7	Preventing		Approved 8,429	ENTEREG

C_max

Value	Dose	Co-administered	Analyte	Population
10.98 ng/mL	12 mg 2 times / day multiple, oral		ALVIMOPAN plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
40.2 ng × h/mL	12 mg 2 times / day multiple, oral		ALVIMOPAN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.5 h	12 mg 2 times / day multiple, oral		ALVIMOPAN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
20%	12 mg 2 times / day multiple, oral		ALVIMOPAN plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
120 mg single, oral Highest studied dose	healthy, adult
48 mg 1 times / day multiple, oral Highest studied dose	healthy, adult
12 mg 2 times / day multiple, oral Recommended	unhealthy, adult
12 mg 2 times / day steady, oral	unhealthy n = 66	Other AEs: Ascites, Ileus...

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AEs

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AE	Significance	Dose	Population
Allergic reaction to chemotherapy	below serious, 1 patient	12 mg 2 times / day steady, oral	unhealthy n = 66
Cystostomy	below serious, 1 patient	12 mg 2 times / day steady, oral	unhealthy n = 66
Dyspepsia	below serious, 1 patient	12 mg 2 times / day steady, oral	unhealthy n = 66
Esophagitis	below serious, 1 patient	12 mg 2 times / day steady, oral	unhealthy n = 66
Gastroparesis	below serious, 1 patient	12 mg 2 times / day steady, oral	unhealthy n = 66

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1,587	inhibitor 1,767 inducer 389	inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1,478 CYP2E1 882 P-gp 1,461	CYP 270 P-gp 1,537	CYP1A2 701 CYP2B6 547 CYP2C19 293 CYP3A4/5 124

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 1,692	inhibitor 3,277	no [IC50 >50 uM]
CYP2A6 739	inhibitor 3,277	no [IC50 >50 uM]
CYP2B6 1,001	inhibitor 3,277	no [IC50 >50 uM]
CYP2C19 1,553	inhibitor 3,277	no [IC50 >50 uM]
CYP2C8 965	inhibitor 3,277	no [IC50 >50 uM]

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3,367	no
P-gp 1,537	substrate 3,367	yes

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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PubMed

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Title	Date	PubMed
		18373729
Alvimopan.	2005 Apr	15882122
Effect of alvimopan and codeine on gastrointestinal transit: a randomized controlled study.	2005 Aug	16234007
Molecule of the month. Alvimopan hydrate.	2005 Jun	16193106
Phase III trial of alvimopan, a novel, peripherally acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery.	2005 Jun	15906123

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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

Show entries

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

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Classification Tree

Code System

Code

Opioid Receptor Interactions

NDF-RT

N0000000154

Peripheral opioid receptor antagonists

WHO-ATC

A06AH02

Agent Affecting Nervous System

NCI_THESAURUS

C681

Established Pharmacologic Class

NDF-RT

N0000175691

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Code System

Code

Type

Description

MERCK INDEX

m1636

PRIMARY

Merck Index

CAS

156053-89-3

PRIMARY

EVMPD

SUB20585

PRIMARY

INN

8245

PRIMARY

SMS_ID

100000085983

PRIMARY

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ACTIVE MOIETY


					Q153V49P3Z

ALVIMOPAN ANHYDROUS

METABOLITE (PARENT)


					3I1G16537O

ADL-08-0011

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator