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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H32N2O4.H2O
Molecular Weight 442.5488
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALVIMOPAN MONOHYDRATE

SMILES

C[C@@]1([H])CN(CC[C@@]1(C)c2cccc(c2)O)C[C@]([H])(Cc3ccccc3)C(=NCC(=O)O)O.O

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 424.5335
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

1.21124159E12
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
Methylnaltrexone and alvimopan: economic management of opioid-induced bowel dysfunction.
2004 Apr
Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus.
2007
Mu opioid receptor antagonists: recent developments.
2007 Nov
Alvimopan accelerates gastrointestinal recovery after bowel resection regardless of age, gender, race, or concomitant medication use.
2007 Oct
Alvimopan: a peripherally acting mu-opioid receptor antagonist.
2007 Sep
Alvimopan.
2008
Opioid-induced constipation in intensive care patients: relief in sight?
2008
Mu-opioid antagonists for opioid-induced bowel dysfunction.
2008 Apr 16
New approaches to the treatment of opioid-induced constipation.
2008 Aug
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
Alvimopan (Entereg) for postoperative ileus.
2008 Dec 1
The involvement of the mu-opioid receptor in gastrointestinal pathophysiology: therapeutic opportunities for antagonism at this receptor.
2008 Jan
Opioid-induced bowel dysfunction.
2008 Jan
Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults.
2008 Jan 23
New therapies in the treatment of postoperative ileus after gastrointestinal surgery.
2008 Jan-Feb
Alvimopan hastens recovery from abdominal surgery.
2008 Jul
New drug to restore bowel function approved under new FDA rules.
2008 Jul 1
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
Alvimopan and COX-2 inhibition reverse opioid and inflammatory components of postoperative ileus.
2008 Jun
Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles.
2008 Mar 15
Pharmacokinetics of alvimopan and its metabolite in healthy volunteers and patients in postoperative ileus trials.
2008 May
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
Alvimopan (Entereg), a Peripherally Acting mu-Opioid Receptor Antagonist For Postoperative Ileus.
2008 Oct
Management of postoperative ileus: focus on alvimopan.
2008 Oct
Postoperative ileus: strategies for reduction.
2008 Oct
Development of peripheral opioid antagonists' new insights into opioid effects.
2008 Oct
Alvimopan.
2008 Sep
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
[News from the cochrane library: mu opioid antagonists for opioid-induced bowel dysfunction].
2008 Sep
Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus.
2008 Sep
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
Economic analysis of alvimopan in North American Phase III efficacy trials.
2009 Aug 1
Peripheral opioid antagonism.
2009 Dec
Pathogenesis and management of postoperative ileus.
2009 Feb
Alvimopan for postoperative ileus: only one piece of the puzzle.
2009 Jul 15
Alvimopan for postoperative ileus.
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
Opioid receptors in the gastrointestinal tract.
2009 Jun 5
An overview of constipation and newer therapies.
2009 Jun-Jul
New drugs 09, part 1.
2009 Oct-Dec
Comment on alvimopan guidelines.
2009 Sep
Pharmacologic options to prevent postoperative ileus.
2009 Sep
Intensive Care Unit-acquired infection as a side effect of sedation.
2010
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
Gastrointestinal recovery after laparoscopic colectomy: results of a prospective, observational, multicenter study.
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 Fri Jun 25 23:56:22 UTC 2021
Edited
by admin
on Fri Jun 25 23:56:22 UTC 2021
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
1383577-62-5
Created by admin on Fri Jun 25 23:56:22 UTC 2021 , Edited by admin on Fri Jun 25 23:56:22 UTC 2021
PRIMARY
PUBCHEM
71587995
Created by admin on Fri Jun 25 23:56:22 UTC 2021 , Edited by admin on Fri Jun 25 23:56:22 UTC 2021
PRIMARY
CAS
1383577-62-5
Created by admin on Fri Jun 25 23:56:22 UTC 2021 , Edited by admin on Fri Jun 25 23:56:22 UTC 2021
PRIMARY
FDA UNII
28LAR2REDG
Created by admin on Fri Jun 25 23:56:22 UTC 2021 , Edited by admin on Fri Jun 25 23:56:22 UTC 2021
PRIMARY
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ACTIVE MOIETY