Details
Stereochemistry | ACHIRAL |
Molecular Formula | C29H33ClN2O2 |
Molecular Weight | 477.038 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C)C(=O)C(CCN1CCC(O)(CC1)C2=CC=C(Cl)C=C2)(C3=CC=CC=C3)C4=CC=CC=C4
InChI
InChIKey=RDOIQAHITMMDAJ-UHFFFAOYSA-N
InChI=1S/C29H33ClN2O2/c1-31(2)27(33)29(24-9-5-3-6-10-24,25-11-7-4-8-12-25)19-22-32-20-17-28(34,18-21-32)23-13-15-26(30)16-14-23/h3-16,34H,17-22H2,1-2H3
Molecular Formula | C29H33ClN2O2 |
Molecular Weight | 477.038 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Loperamide is a commonly used over-the-counter (OTC) and prescription medicine that is approved to help control symptoms of diarrhea, including Travelers’ Diarrhea. The maximum approved daily dose for adults is 8 mg per day for OTC use and 16 mg per day for prescription use. It is sold under the OTC brand name Imodium A-D, as store brands, and as generics. In vitro and animal studies show that IMODIUM® (loperamide hydrochloride) acts by slowing
intestinal motility and by affecting water and electrolyte movement through the bowel.
Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of
acetylcholine and prostaglandins, thereby reducing propulsive peristalsis, and increasing
intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency. Loperamide is also indicated for reducing the volume of discharge from ileostomies. In man, Loperamide prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed. Loperamide is an opioid receptor agonist and acts on the mu opioid receptors in the myenteric plexus large intestines; it does not affect the central nervous system like other opioids. It works specifically by decreasing the activity of the myenteric plexus which decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall. This increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the fecal matter. Loperamide also decreases colonic mass movements and suppresses the gastrocolic reflex.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27918873
Curator's Comment: Loperamide was first synthesized by Paul Janssen of Janssen Pharmaceutica in 1969
Approval Year
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.24 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/438356 |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
LOPERAMIDE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
26.1 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/438356 |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
LOPERAMIDE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/438356 |
8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered: |
LOPERAMIDE blood | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
10.8 h |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
LOPERAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5% |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
LOPERAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg 2 times / day multiple, oral Overdose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, 26 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 26 Sex: M Population Size: 1 Sources: |
Disc. AE: Cardiac arrest... AEs leading to discontinuation/dose reduction: Cardiac arrest (grade 5) Sources: |
792 mg 1 times / day multiple, oral (total daily dose) Overdose Dose: 792 mg, 1 times / day Route: oral Route: multiple Dose: 792 mg, 1 times / day Sources: Page: p.954 |
unhealthy, 28 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 28 Sex: M Population Size: 1 Sources: Page: p.954 |
Disc. AE: Syncope, Tachycardia... AEs leading to discontinuation/dose reduction: Syncope Sources: Page: p.954Tachycardia Electrocardiogram QTc interval prolonged Cardiac arrest |
400 mg 1 times / day multiple, oral Overdose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 30 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 30 Sex: M Population Size: 1 Sources: |
Disc. AE: Syncope, Cardiac arrest... AEs leading to discontinuation/dose reduction: Syncope Sources: Cardiac arrest Torsades de pointes |
16 mg 8 times / day multiple, oral (total daily dose) Recommended Dose: 16 mg, 8 times / day Route: oral Route: multiple Dose: 16 mg, 8 times / day Sources: Page: p.1, 3 |
unhealthy Health Status: unhealthy Condition: Diarrhea Sources: Page: p.1, 3 |
Disc. AE: Torsades de pointes, Cardiac arrest... AEs leading to discontinuation/dose reduction: Torsades de pointes Sources: Page: p.1, 3Cardiac arrest |
16 mg 8 times / day multiple, oral (total daily dose) Recommended Dose: 16 mg, 8 times / day Route: oral Route: multiple Dose: 16 mg, 8 times / day Sources: Page: p.3 |
unhealthy Health Status: unhealthy Condition: Diarrhea Sources: Page: p.3 |
Disc. AE: Ventricular tachycardia, Syncope... AEs leading to discontinuation/dose reduction: Ventricular tachycardia Sources: Page: p.3Syncope |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Cardiac arrest | grade 5 Disc. AE |
400 mg 2 times / day multiple, oral Overdose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
unhealthy, 26 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 26 Sex: M Population Size: 1 Sources: |
Cardiac arrest | Disc. AE | 792 mg 1 times / day multiple, oral (total daily dose) Overdose Dose: 792 mg, 1 times / day Route: oral Route: multiple Dose: 792 mg, 1 times / day Sources: Page: p.954 |
unhealthy, 28 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 28 Sex: M Population Size: 1 Sources: Page: p.954 |
Electrocardiogram QTc interval prolonged | Disc. AE | 792 mg 1 times / day multiple, oral (total daily dose) Overdose Dose: 792 mg, 1 times / day Route: oral Route: multiple Dose: 792 mg, 1 times / day Sources: Page: p.954 |
unhealthy, 28 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 28 Sex: M Population Size: 1 Sources: Page: p.954 |
Syncope | Disc. AE | 792 mg 1 times / day multiple, oral (total daily dose) Overdose Dose: 792 mg, 1 times / day Route: oral Route: multiple Dose: 792 mg, 1 times / day Sources: Page: p.954 |
unhealthy, 28 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 28 Sex: M Population Size: 1 Sources: Page: p.954 |
Tachycardia | Disc. AE | 792 mg 1 times / day multiple, oral (total daily dose) Overdose Dose: 792 mg, 1 times / day Route: oral Route: multiple Dose: 792 mg, 1 times / day Sources: Page: p.954 |
unhealthy, 28 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 28 Sex: M Population Size: 1 Sources: Page: p.954 |
Cardiac arrest | Disc. AE | 400 mg 1 times / day multiple, oral Overdose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 30 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 30 Sex: M Population Size: 1 Sources: |
Syncope | Disc. AE | 400 mg 1 times / day multiple, oral Overdose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 30 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 30 Sex: M Population Size: 1 Sources: |
Torsades de pointes | Disc. AE | 400 mg 1 times / day multiple, oral Overdose Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: |
unhealthy, 30 n = 1 Health Status: unhealthy Condition: Opiate abuse Age Group: 30 Sex: M Population Size: 1 Sources: |
Cardiac arrest | Disc. AE | 16 mg 8 times / day multiple, oral (total daily dose) Recommended Dose: 16 mg, 8 times / day Route: oral Route: multiple Dose: 16 mg, 8 times / day Sources: Page: p.1, 3 |
unhealthy Health Status: unhealthy Condition: Diarrhea Sources: Page: p.1, 3 |
Torsades de pointes | Disc. AE | 16 mg 8 times / day multiple, oral (total daily dose) Recommended Dose: 16 mg, 8 times / day Route: oral Route: multiple Dose: 16 mg, 8 times / day Sources: Page: p.1, 3 |
unhealthy Health Status: unhealthy Condition: Diarrhea Sources: Page: p.1, 3 |
Syncope | Disc. AE | 16 mg 8 times / day multiple, oral (total daily dose) Recommended Dose: 16 mg, 8 times / day Route: oral Route: multiple Dose: 16 mg, 8 times / day Sources: Page: p.3 |
unhealthy Health Status: unhealthy Condition: Diarrhea Sources: Page: p.3 |
Ventricular tachycardia | Disc. AE | 16 mg 8 times / day multiple, oral (total daily dose) Recommended Dose: 16 mg, 8 times / day Route: oral Route: multiple Dose: 16 mg, 8 times / day Sources: Page: p.3 |
unhealthy Health Status: unhealthy Condition: Diarrhea Sources: Page: p.3 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/16415122/ Page: 1.0 |
strong [IC50 0.05 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 2.0 |
minor | |||
Page: 2.0 |
minor | |||
yes | ||||
Page: 2.0 |
yes | yes (co-administration study) Comment: single 4-mg dose of loperamide hydrochloride was co-administered with 600 mg gemfibrozil, a strong inhibitor of CYP2C8, on day 3 of a 5-day treatment with gemfibrozil twice daily, the mean peak plasma concentration and the systemic exposure to loperamide was increased by 1.6-fold and 2.2-fold, respectively Page: 2.0 |
||
Page: 2.0 |
yes | yes (co-administration study) Comment: Concomitant administration of multiple doses of 100 mg itraconazole twice daily, an inhibitor of both CYP3A4, with a single 4-mg dose of loperamide hydrochloride increased the peak plasma concentration and the systemic exposure to loperamide by 2.9-fold and 3.8-fold, respectively Page: 2.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Interactions between herbal medicines and prescribed drugs: a systematic review. | 2001 |
|
Therapeutic response to octreotide in patients with refractory CPT-11 induced diarrhea. | 2001 |
|
Assessment of cure and recurrence after pituitary surgery for Cushing's disease. | 2001 |
|
Increase of opioid mu-receptor gene expression in streptozotocin-induced diabetic rats. | 2001 Aug |
|
Effects of loperamide and other opioid-related substances on the transcriptional regulation of the rat pro-opiomelanocortin gene in AtT20 cells. | 2001 Aug |
|
[Irritable colon]. | 2001 Aug 20 |
|
Effects of yogurt supplemented with brewer's yeast cell wall on constipation and intestinal microflora in rats. | 2001 Dec |
|
Treatment options for fecal incontinence. | 2001 Jan |
|
[Loperamide abuse in anxiety disorder]. | 2001 Jul |
|
Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance. | 2001 Jul |
|
Optimal dosing of ofloxacin with loperamide in the treatment of non-dysenteric travelers' diarrhea. | 2001 Jul-Aug |
|
Does loperamide affect motor activity after proctocolectomy and ileal pouch-anal anastomosis? An experimental study in dogs. | 2001 Jun |
|
Ritonavir increases loperamide plasma concentrations without evidence for P-glycoprotein involvement. | 2001 Nov |
|
[Colonic microflora and motility. Physiological data and during irritable bowel syndrome]. | 2001 Sep |
|
Traveler's diarrhea. | 2001 Sep |
|
Clinical evaluation and management of acute infectious diarrhea in adults. | 2001 Sep |
|
Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. | 2002 Apr |
|
Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of collies from the northwestern United States. | 2002 Apr |
|
Spinal and peripheral mu opioids and the development of secondary tactile allodynia after thermal injury. | 2002 Apr |
|
Irinotecan in relapsed or refractory non-Hodgkin's lymphomas. Indications of activity in a phase II trial. | 2002 Aug |
|
A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. | 2002 Aug 12 |
|
New mu-opioid receptor agonists with phenoxyacetic acid moiety. | 2002 Feb |
|
Comparison of the peripheral and central effects of the opioid agonists loperamide and morphine in the formalin test in rats. | 2002 Feb |
|
K+ channel cAMP activated in guinea pig gallbladder epithelial cells. | 2002 Feb 8 |
|
Acute gastroenteritis in children. | 2002 Jun |
|
Laxative and anti-diarrheal activity of polycarbophil in mice and rats. | 2002 Jun |
|
Fumagillin treatment of intestinal microsporidiosis. | 2002 Jun 20 |
|
Fecal incontinence in anorectal malformations, neuropathy, and miscellaneous conditions. | 2002 May |
|
Lymphocytic colitis: clinical features, treatment, and outcomes. | 2002 Nov |
|
Spreading depression: imaging and blockade in the rat neocortical brain slice. | 2002 Nov |
|
Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. | 2002 Nov 4 |
|
Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer. | 2002 Nov-Dec |
|
New developments in the diagnosis and treatment of irritable bowel syndrome. | 2002 Oct |
|
Antipruritic and antihyperalgesic actions of loperamide and analogs. | 2002 Oct 25 |
|
Irinotecan, cisplatin and mitomycin in inoperable gastro-oesophageal and pancreatic cancers - a new active regimen. | 2002 Oct 7 |
|
[Taking charge of adult's anal incontinence]. | 2002 Sep |
|
[Travellers' acute diarrhea]. | 2002 Sep |
|
Antidiarrhoeal activity of seed extract of Albizzia lebbeck Benth. | 2002 Sep |
|
Dose-response relationship and mechanism of action of Saccharomyces boulardii in castor oil-induced diarrhea in rats. | 2003 Apr |
|
Effect of loperamide on gastro-oesophageal reflux. | 2003 Apr |
|
Pharmacologic therapy for the irritable bowel syndrome. | 2003 Apr |
|
Cost of illness in the 1993 waterborne Cryptosporidium outbreak, Milwaukee, Wisconsin. | 2003 Apr |
|
Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. | 2003 Apr 22 |
|
Morphine and d-amphetamine nullify each others' hypothermic effects in mice. | 2003 Feb |
|
Travellers' diarrhoea. | 2003 Feb |
|
Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. | 2003 Jun 18 |
|
Evaluation of different calorimetric methods to determine the glass transition temperature and molecular mobility below T(g) for amorphous drugs. | 2003 Jun 18 |
|
[Malaria--case report]. | 2003 Jun 6 |
|
EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer. | 2003 Mar 10 |
|
Loperamide mobilizes intracellular Ca2+ stores in insulin-secreting HIT-T15 cells. | 2003 May |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/loperamide.html
Usual Adult Dose for Diarrhea - Acute
Tablets, capsules, and liquid:
Initial: 4 mg orally after the first loose stool, then
Maintenance: 2 mg after each loose stool, not to exceed 16 mg in any 24-hour period. Clinical improvement is usually observed within 48 hours.
Chewable tablets:
Initial: 4 mg after the first loose stool, then
Maintenance: 2 mg after each subsequent loose stool, but not exceeding 8 mg in 24 hours.
Usual Adult Dose for Diarrhea - Chronic
Tablets, capsules, and liquid:
Initial: 4 mg orally once followed by 2 mg orally after each loose stool, not to exceed 16 mg in any 24-hour period.
Maintenance: The average daily maintenance dosage is 4 to 8 mg. Clinical improvement is usually observed within 10 days. If clinical improvement is not observed at a maximum dosage of 16 mg for duration of 10 days, symptoms are unlikely to be controlled by further administration.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11021978
Loperamide caused a concentration-dependent inhibition of the ascending contractile reflex response in the rat ileum with an IC(50) of 1.4x10(-7)M
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:42:34 GMT 2023
by
admin
on
Fri Dec 15 15:42:34 GMT 2023
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Record UNII |
6X9OC3H4II
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Record Status |
Validated (UNII)
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Record Version |
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WHO-VATC |
QA07DA03
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WHO-ATC |
A07DA53
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A07DA03
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NCI_THESAURUS |
C1506
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NDF-RT |
N0000175690
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NCI_THESAURUS |
C266
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N0000000174
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LIVERTOX |
NBK547935
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WHO-VATC |
QA07DA53
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53179-11-6
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LOPERAMIDE
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Loperamide
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m6898
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258-416-5
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TRANSPORTER -> SUBSTRATE |
In vitro ER in the MDCKII-MDR1 cells t from Netherlands Cancer Institute (NKI; Borst cell line)
EFFLUX RATIO
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TRANSPORTER -> SUBSTRATE |
Dogs with the ABCB1-1Δ mutation are at risk of developing a severe neurotoxicosis with standard doses of loperamide.
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METABOLIC ENZYME -> INHIBITOR |
IC50
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BINDER->LIGAND |
BINDING
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> SUBSTRATE |
in vitro ER in the MDCK-MDR1 cell line from National Institutes of Health
EFFLUX RATIO
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Related Record | Type | Details | ||
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METABOLITE ACTIVE -> PARENT |
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METABOLITE ACTIVE -> PARENT |
MAJOR
PLASMA
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METABOLITE ACTIVE -> PARENT |
MAJOR
PLASMA
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PRODRUG -> METABOLITE ACTIVE |
Related Record | Type | Details | ||
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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