Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C24H29N5O3 |
Molecular Weight | 435.5188 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCC(=O)N(CC1=CC=C(C=C1)C2=C(C=CC=C2)C3=NN=NN3)[C@@H](C(C)C)C(O)=O
InChI
InChIKey=ACWBQPMHZXGDFX-QFIPXVFZSA-N
InChI=1S/C24H29N5O3/c1-4-5-10-21(30)29(22(16(2)3)24(31)32)15-17-11-13-18(14-12-17)19-8-6-7-9-20(19)23-25-27-28-26-23/h6-9,11-14,16,22H,4-5,10,15H2,1-3H3,(H,31,32)(H,25,26,27,28)/t22-/m0/s1
Molecular Formula | C24H29N5O3 |
Molecular Weight | 435.5188 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/entresto.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/25052956http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdfCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/mesh/2009869
Sources: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/entresto.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/25052956http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021283s50lbl.pdf
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/mesh/2009869
Valsartan (DIOVAN®) is a tetrazole derivative, and specific angiotensin II type 1 (AT1) receptor blocker that is indicated for the treatment of hypertension, to lower blood pressure. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme. Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Valsartan (DIOVAN®) blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26663387https://www.ncbi.nlm.nih.gov/pubmed/23227311
Curator's Comment: LBQ657 (an LCZ696 metabolite) achieves CSF concentrations sufficient to inhibit neprilysin, but LCZ696 did not cause changes in CSF levels of aggregable Abeta isoforms (1-42 and 1-40) compared with placebo
Originator
Sources: https://www.novartis.com/news/media-releases/novartis-new-heart-failure-medicine-lcz696-now-called-entrestotm-approved-fdahttps://www.ncbi.nlm.nih.gov/pubmed/8505092
Curator's Comment: # Novartis
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL227 |
2.38 nM [Ki] | ||
Target ID: CHEMBL1944 |
2.3 nM [IC50] | ||
Target ID: CHEMBL227 |
2.43 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ENTRESTO Approved UseENTRESTO is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker, indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB. Launch Date2015 |
|||
Primary | DIOVAN Approved UseDiovan is an angiotensin II receptor blocker (ARB) indicated for:
Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1)
Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2)
Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date2011 |
|||
Primary | DIOVAN Approved UseDiovan is an angiotensin II receptor blocker (ARB) indicated for:
Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1)
Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2)
Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date2011 |
|||
Palliative | DIOVAN Approved UseDiovan is an angiotensin II receptor blocker (ARB) indicated for:
Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions (1.1)
Treatment of heart failure (NYHA class II-IV); Diovan significantly reduced hospitalization for heart failure (1.2)
Reduction of cardiovascular mortality in clinically stable patients with left ventricular failure or left ventricular dysfunction following myocardial infarction (1.3) Launch Date2011 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2808 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5756 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2.141 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777 |
160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
20650 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
34310 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
22.56 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777 |
160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
8.45 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27128457 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
9.55 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21617777 |
160 mg single, oral dose: 160 mg route of administration: Oral experiment type: SINGLE co-administered: |
VALSARTAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2.24 mg single, oral Overdose |
unknown, 25 years n = 1 Health Status: unknown Age Group: 25 years Sex: F Population Size: 1 Sources: |
Other AEs: Muscle cramps... |
640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Disc. AE: Hyperkalemia... Other AEs: Dizziness, Headache... AEs leading to discontinuation/dose reduction: Hyperkalemia (1 patient) Other AEs:Dizziness (8.3%) Sources: Headache (9.2%) Back pain (5.8%) Upper respiratory tract infection (5.8%) Nasopharyngitis (5%) Diarrhea (5%) Hypoglycemia (5%) Peripheral edema (4.2%) Nausea (4.2%) |
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
pregnant Health Status: pregnant Sources: |
Disc. AE: Disorder fetal... AEs leading to discontinuation/dose reduction: Disorder fetal Sources: |
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy n = 2316 Health Status: unhealthy Condition: hypertension Population Size: 2316 Sources: |
Disc. AE: Headache, Dizziness... AEs leading to discontinuation/dose reduction: Headache (2.3%) Sources: Dizziness (2.3%) |
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy n = 2506 Health Status: unhealthy Condition: Heart Failure Population Size: 2506 Sources: |
Disc. AE: Creatinine increased, Potassium increased... AEs leading to discontinuation/dose reduction: Creatinine increased (0.5%) Sources: Potassium increased (0.5%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Muscle cramps | 1 patient | 2.24 mg single, oral Overdose |
unknown, 25 years n = 1 Health Status: unknown Age Group: 25 years Sex: F Population Size: 1 Sources: |
Hyperkalemia | 1 patient Disc. AE |
640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Nausea | 4.2% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Peripheral edema | 4.2% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Diarrhea | 5% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Hypoglycemia | 5% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Nasopharyngitis | 5% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Back pain | 5.8% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Upper respiratory tract infection | 5.8% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Dizziness | 8.3% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Headache | 9.2% | 640 mg 1 times / day steady, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: steady Dose: 640 mg, 1 times / day Sources: |
unhealthy, 57.5 years n = 131 Health Status: unhealthy Age Group: 57.5 years Sex: M+F Population Size: 131 Sources: |
Disorder fetal | Disc. AE | 320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
pregnant Health Status: pregnant Sources: |
Dizziness | 2.3% Disc. AE |
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy n = 2316 Health Status: unhealthy Condition: hypertension Population Size: 2316 Sources: |
Headache | 2.3% Disc. AE |
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy n = 2316 Health Status: unhealthy Condition: hypertension Population Size: 2316 Sources: |
Creatinine increased | 0.5% Disc. AE |
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy n = 2506 Health Status: unhealthy Condition: Heart Failure Population Size: 2506 Sources: |
Potassium increased | 0.5% Disc. AE |
320 mg 1 times / day steady, oral Recommended Dose: 320 mg, 1 times / day Route: oral Route: steady Dose: 320 mg, 1 times / day Sources: |
unhealthy n = 2506 Health Status: unhealthy Condition: Heart Failure Population Size: 2506 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Angiotensin II receptor blockade with single doses of valsartan in healthy, normotensive subjects. | 1994 |
|
Remodelling of resistance arteries in genetically hypertensive rats by treatment with valsartan, an angiotensin II receptor antagonist. | 1996 Jun-Jul |
|
Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine. | 1996 Sep |
|
LCZ696 : a new paradigm for the treatment of heart failure? | 2015 Feb |
|
Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction. | 2016 Aug |
Sample Use Guides
The recommended starting dose of ENTRESTO, previously known as LCZ696, is 49/51 mg (sacubitril/valsartan) twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg (sacubitril/valsartan) twice-daily, as tolerated by the patient.
Route of Administration:
Oral
In Vitro Use Guide
Sources: Von Lueder TG, Wang B, Kompa A, Huang L, Webb R, Jordan P, Krum H. ARNi, combined neprilysin and angiotensin receptor inhibition augments anti-fibrotic and anti-hypertrophic effects in vitro. Eur.Heart J. 2012;33:P5834.
Curator's Comment: ...
30 nM to 1 uM valsartan (LCZ696 component) in the presence of 10 uM LBQ657 (Sacubitril (LCZ696 component) metabolite) demonstrate anti-fibrotic and anti-hypertrophic effects on rat cardiac fibroblasts and cardiomyocytes, respectively, cultured with 100 nM angiotensin II
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 16:30:46 GMT 2023
by
admin
on
Fri Dec 15 16:30:46 GMT 2023
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Record UNII |
80M03YXJ7I
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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WHO-ATC |
C09CA03
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EMA ASSESSMENT REPORTS |
IMPRADA-HCT (WITHDRAWN: HYPERTENSION)
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WHO-ATC |
C10BX10
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EMA ASSESSMENT REPORTS |
EXFORGE (AUTHORIZED: HYPERTENSION)
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FDA ORPHAN DRUG |
494115
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WHO-VATC |
QC09CA03
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NDF-RT |
N0000175561
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WHO-ATC |
C09DX02
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EMA ASSESSMENT REPORTS |
COPALIA (AUTHORIZED: HYPERTENSION)
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WHO-ATC |
C09DX01
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WHO-VATC |
QC09DA03
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EMA ASSESSMENT REPORTS |
EXFORGE-HCT (AUTHORIZED: HYPERTENSION)
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NCI_THESAURUS |
C66930
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WHO-ATC |
C09DB08
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EMA ASSESSMENT REPORTS |
DARFIRO-HCT (AUTHORIZED: HYPERTENSION)
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LIVERTOX |
NBK547944
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COPALIA-HCT (AUTHORIZED: HYPERTENSION)
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WHO-ATC |
C09DA03
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NDF-RT |
N0000000070
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DAFIRO (AUTHORIZED: HYPERTENSION)
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WHO-VATC |
QC09DX01
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EMA ASSESSMENT REPORTS |
IMPRIDA (AUTHORIZED: HYPERTENSION)
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WHO-ATC |
C09DX05
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WHO-ATC |
C09DX04
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QC09DX02
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WHO-ATC |
C09DB01
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WHO-VATC |
QC09DB01
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C47781
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Valsartan
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admin on Fri Dec 15 16:30:46 GMT 2023 , Edited by admin on Fri Dec 15 16:30:46 GMT 2023
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9927
Created by
admin on Fri Dec 15 16:30:46 GMT 2023 , Edited by admin on Fri Dec 15 16:30:46 GMT 2023
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HH-50
Created by
admin on Fri Dec 15 16:30:46 GMT 2023 , Edited by admin on Fri Dec 15 16:30:46 GMT 2023
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m11372
Created by
admin on Fri Dec 15 16:30:46 GMT 2023 , Edited by admin on Fri Dec 15 16:30:46 GMT 2023
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60846
Created by
admin on Fri Dec 15 16:30:46 GMT 2023 , Edited by admin on Fri Dec 15 16:30:46 GMT 2023
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SUB00017MIG
Created by
admin on Fri Dec 15 16:30:46 GMT 2023 , Edited by admin on Fri Dec 15 16:30:46 GMT 2023
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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BINDER->LIGAND |
BINDING
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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TRANSPORTER -> INHIBITOR | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
EP
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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METABOLITE INACTIVE -> PARENT | |||
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METABOLITE INACTIVE -> PARENT |
Valsartan was metabolized to a small extent only. The only notable metabolite in plasma, urine and faecs
MAJOR
FECAL; PLASMA; URINE
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
Probable human carcinogen.
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
UNSPECIFIED
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT | |||
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IMPURITY -> PARENT |
Priority toxic pollutant.
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
NDMA is an organic chemical that is in a family of potent carcinogens.
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Route of Elimination | PHARMACOKINETIC |
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ROUTE OF ADMINISTRATION: ORAL |
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MAXIMUM TOLERATED DOSE | TOXICITY |
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PROTEIN BINDING | PHARMACOKINETIC |
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Route of Elimination | PHARMACOKINETIC |
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ROUTE OF ADMINISTRATION: ORAL |
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RENAL CLEARANCE | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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