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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H28N5O3.Na
Molecular Weight 457.5006
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VALSARTAN MONOSODIUM

SMILES

[Na+].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=KVPFCQWDTYOLIK-FTBISJDPSA-M
InChI=1S/C24H29N5O3.Na/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);/q;+1/p-1/t22-;/m0./s1

HIDE SMILES / InChI

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C24H28N5O3
Molecular Weight 434.5108
Charge -1
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

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

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ENTRESTO

Approved Use

ENTRESTO 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 Date

2015
Primary
DIOVAN

Approved Use

Diovan 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 Date

2011
Primary
DIOVAN

Approved Use

Diovan 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 Date

2011
Palliative
DIOVAN

Approved Use

Diovan 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 Date

2011
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2808 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
20650 ng × h/mL
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
8.45 h
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
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
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

Doses

DosePopulationAdverse events​
2.24 mg single, oral
Overdose
Dose: 2.24 mg
Route: oral
Route: single
Dose: 2.24 mg
Sources:
unknown, 25 years
n = 1
Health Status: unknown
Age Group: 25 years
Sex: F
Population Size: 1
Sources:
Other AEs: Muscle cramps...
Other AEs:
Muscle cramps (1 patient)
Sources:
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%)
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%)
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:
pregnant
Disc. AE: Disorder fetal...
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%)
Dizziness (2.3%)
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 = 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%)
Potassium increased (0.5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Muscle cramps 1 patient
2.24 mg single, oral
Overdose
Dose: 2.24 mg
Route: oral
Route: single
Dose: 2.24 mg
Sources:
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
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

PubMed

TitleDatePubMed
Angiotensin II receptor blockade with single doses of valsartan in healthy, normotensive subjects.
1994
Development and validation of chiral high-performance liquid chromatographic methods for the quantitation of valsartan and of the tosylate of valinebenzyl ester.
1996 Nov 8
Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.
2014 Apr
Determination of the R-enantiomer of valsartan in pharmaceutical formulation by capillary electrophoresis.
2015
LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice.
2016 Apr
Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial.
2016 Mar
Patents

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 Sat Dec 16 18:54:53 GMT 2023
Edited
by admin
on Sat Dec 16 18:54:53 GMT 2023
Record UNII
D6XN347U2D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VALSARTAN MONOSODIUM
Common Name English
L-VALINE, N-(1-OXOPENTYL)-N-((2'-(2H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-, SODIUM SALT (1:1)
Systematic Name English
VALSARTAN SODIUM SALT
Common Name English
Code System Code Type Description
PUBCHEM
23682221
Created by admin on Sat Dec 16 18:54:54 GMT 2023 , Edited by admin on Sat Dec 16 18:54:54 GMT 2023
PRIMARY
CAS
1178578-85-2
Created by admin on Sat Dec 16 18:54:54 GMT 2023 , Edited by admin on Sat Dec 16 18:54:54 GMT 2023
NON-SPECIFIC STOICHIOMETRY
CAS
391231-02-0
Created by admin on Sat Dec 16 18:54:54 GMT 2023 , Edited by admin on Sat Dec 16 18:54:54 GMT 2023
PRIMARY
FDA UNII
D6XN347U2D
Created by admin on Sat Dec 16 18:54:54 GMT 2023 , Edited by admin on Sat Dec 16 18:54:54 GMT 2023
PRIMARY
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ACTIVE MOIETY