General
Preferred name
VALSARTAN
Synonyms
Valsartan D9 ()
CGP-48933 D9 ()
CGP 48933 ()
Diovan ()
Tareg ()
LCZ-696 ()
Valsartan (CGP-48933) ()
CGP-48933 ()
Exforge ()
NSC-758927 ()
Prexxartan ()
Valsartan-d9 ()
P&D ID
PD000563
CAS
137862-53-4
1089736-73-1
Tags
natural product
drug
available
Approved by
PMDA
EMA
FDA
First approval
1996
Drug Status
investigational
approved
Drug indication
Hypertension
Antihypertensive
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE After intravenous (IV) administration, valsartan demonstrates bi-exponential decay kinetics (t1/2α <1 hour and t1/2β between 5-9 hours) [F3139].
PHARMACODYNAMICS Valsartan inhibits the pressor effect of an angiotensin II hormone, decreasing blood pressure [F3139]. Angiotensin II is formed from angiotensin I during a reaction that is catalyzed by angiotensin-converting enzyme, also known as _ACE_ . Angiotensin II is the main pressor agent of the renin-angiotensin system, causing vasoconstriction, aldosterone synthesis and release, cardiac stimulation, as well as the renal reabsorption of sodium [FDA label]. The cardioprotective benefits of valsartan have been shown in large-scale clinical outcomes trials and include significant decreases in cardiovascular morbidity and mortality in heart failure, after myocardial infarction, and in patients with comorbid hypertension and coronary artery disease and/or heart failure; reductions in heart failure hospitalizations; and reductions in stroke incidence [FDA label], [A174124]. This drug has been shown to slow the progression of diabetic nephropathy due to its renoprotective effects [A174157], [A174160], [A174163]. Improvements in chronic kidney disease with valsartan include both clinically and statistically significant decreases in urinary albumin and protein excretion in patients diagnosed with type 2 diabetes and in nondiabetic patients diagnosed with chronic kidney disease [A174124].
ROE Valsartan, when administered as an oral solution, is mostly recovered in the feces (about 83% of dose) and urine (about 13% of dose). Unchanged drug is mainly recovered, with only about 20% of dose measured as metabolites. The primary metabolite, accounting for about 10% of dose, is _valeryl 4-hydroxy valsarta_n. The main enzyme(s) responsible for valsartan metabolism have not been elucidated but do not appear to be CYP 450 isozymes [F3139].
MOA Valsartan selectively acts on _AT1_, the subtype receptor that mediates the cardiovascular actions of angiotensin II, the main vasoactive hormone of the renin-angiotensin-system. The _AT2_ receptor subtype, which can be found in tissues such as the brain, endometrium, myometrium, and fetal kidney and adrenals, plays no known role in cardiovascular homeostasis at this time [F3139]. Angiotensin II contributes to vasoconstrictor activity and sodium/water retention, which contribute to hypertension. Through the inhibition of response to angiotensin II by actions on the _AT1_ receptor, valsartan is able to decrease blood pressure [FDA label]. The cardioprotective effects of valsartan are thought to occur through inverse agonist activity of valsartan on the _AT1_ receptor, which plays an important role in cardiac remodeling (causing ventricular hypertrophy). Inverse agonists such as valsartan inactivate this receptor, preventing cardiovascular remodeling [A174154].
INDICATION **Monotherapy** Valsartan may be used alone for the management of hypertension [FDA label] **Combination therapy** Valsartan is indicated for the management of hypertension in patients for whom combination therapy is deemed appropriate [F3139]. It is combined with other anthypertensive agents such as hydrochlorothiazide, amlodipine, nevibolol and sacubitril [F3139], [F3136], [F3145], [F3148]. **Heart Failure** Valsartan is indicated for the treatment of heart failure (NYHA class II-IV) in patients who are intolerant to angiotensin-converting enzyme inhibitors (ACE inhibitors) for various reasons, including those who experience ACE inhibitor adverse effects. In a clinical study of 5010 patients, hospitalizations due to heart failure were markedly decreased when valsartan was taken regularly over a 2-year span [FDA label].
TOXICITY Approximate LD50 >2000 mg/kg (Gavage, rat) [F3139] **A note on hyperkalemia**: This drug may cause hyperkalemia, thus, monitoring of potassium is warranted, especially in patients with nephropathy [A174127]. A full list of adverse events is available in the "Adverse Effects" section of this drug entry. **Reproductive Toxicology Studies** No teratogenic effects were seen when valsartan was given to pregnant mice and rats at oral doses up to 600 mg/kg/day and to pregnant rabbits at oral doses reaching up to 10 mg/kg/day. Despite this, marked decreases in fetal weight, pup birth weight, pup survival rate, and delays in developmental milestones were noted in studies in which parental rats were treated with valsartan at oral, maternally toxic doses of 600 mg/kg/day during the organogenesis period or during late gestation and lactation [FDA label]. **Pregnancy** When used in pregnancy, drugs that act directly on the renin-angiotensin system (RAAS) can cause injury and death to the developing fetus. When pregnancy is detected, valsartan should be discontinued as soon as possible [FDA label].
METABOLISM This drug undergoes minimal liver metabolism [A174124]. Valsartan is not biotransformed to a high degree, as only approximately 20% of a single dose is recovered as metabolites. A hydroxyl metabolite has been found in plasma at low concentrations (less than 10% of the valsartan area under the curve). This metabolite is inactive [F3139].
PHARMACODYNAMICS Valsartan inhibits the pressor effect of an angiotensin II hormone, decreasing blood pressure [F3139]. ; ; Angiotensin II is formed from angiotensin I during a reaction that is catalyzed by angiotensin-converting enzyme, also known as _ACE_ . Angiotensin II is the main pressor agent of the renin-angiotensin system, causing vasoconstriction, aldosterone synthesis and release, cardiac stimulation, as well as the renal reabsorption of sodium [FDA label].; ; The cardioprotective benefits of valsartan have been shown in large-scale clinical outcomes trials and include significant decreases in cardiovascular morbidity and mortality in heart failure, after myocardial infarction, and in patients with comorbid hypertension and coronary artery disease and/or heart failure; reductions in heart failure hospitalizations; and reductions in stroke incidence [FDA label], [A174124]. ; ; This drug has been shown to slow the progression of diabetic nephropathy due to its renoprotective effects [A174157], [A174160], [A174163]. Improvements in chronic kidney disease with valsartan include both clinically and statistically significant decreases in urinary albumin and protein excretion in patients diagnosed with type 2 diabetes and in nondiabetic patients diagnosed with chronic kidney disease [A174124].
MOA Valsartan selectively acts on _AT1_, the subtype receptor that mediates the cardiovascular actions of angiotensin II, the main vasoactive hormone of the renin-angiotensin-system. The _AT2_ receptor subtype, which can be found in tissues such as the brain, endometrium, myometrium, and fetal kidney and adrenals, plays no known role in cardiovascular homeostasis at this time [F3139].; ; Angiotensin II contributes to vasoconstrictor activity and sodium/water retention, which contribute to hypertension. Through the inhibition of response to angiotensin II by actions on the _AT1_ receptor, valsartan is able to decrease blood pressure [FDA label].; ; The cardioprotective effects of valsartan are thought to occur through inverse agonist activity of valsartan on the _AT1_ receptor, which plays an important role in cardiac remodeling (causing ventricular hypertrophy). Inverse agonists such as valsartan inactivate this receptor, preventing cardiovascular remodeling [A174154].
INDICATION **Monotherapy**; ; Valsartan may be used alone for the management of hypertension [FDA label]; ; **Combination therapy**; ; Valsartan is indicated for the management of hypertension in patients for whom combination therapy is deemed appropriate [F3139]. It is combined with other anthypertensive agents such as hydrochlorothiazide, amlodipine, nevibolol and sacubitril [F3139], [F3136], [F3145], [F3148].; ; **Heart Failure**; ; Valsartan is indicated for the treatment of heart failure (NYHA class II-IV) in patients who are intolerant to angiotensin-converting enzyme inhibitors (ACE inhibitors) for various reasons, including those who experience ACE inhibitor adverse effects. In a clinical study of 5010 patients, hospitalizations due to heart failure were markedly decreased when valsartan was taken regularly over a 2-year span [FDA label].; ; ;
TOXICITY Approximate LD50 >2000 mg/kg (Gavage, rat) [F3139]; ; **A note on hyperkalemia**: This drug may cause hyperkalemia, thus, monitoring of potassium is warranted, especially in patients with nephropathy [A174127]. A full list of adverse events is available in the "Adverse Effects" section of this drug entry.; ; **Reproductive Toxicology Studies**; ; No teratogenic effects were seen when valsartan was given to pregnant mice and rats at oral doses up to 600 mg/kg/day and to pregnant rabbits at oral doses reaching up to 10 mg/kg/day. Despite this, marked decreases in fetal weight, pup birth weight, pup survival rate, and delays in developmental milestones were noted in studies in which parental rats were treated with valsartan at oral, maternally toxic doses of 600 mg/kg/day during the organogenesis period or during late gestation and lactation [FDA label].; ; **Pregnancy**; ; When used in pregnancy, drugs that act directly on the renin-angiotensin system (RAAS) can cause injury and death to the developing fetus. When pregnancy is detected, valsartan should be discontinued as soon as possible [FDA label].
METABOLISM This drug undergoes minimal liver metabolism [A174124]. Valsartan is not biotransformed to a high degree, as only approximately 20% of a single dose is recovered as metabolites. A hydroxyl metabolite has been found in plasma at low concentrations (less than 10% of the valsartan area under the curve). This metabolite is inactive [F3139].;
ABSORPTION Absolute bioavailability for valsartan is approximately 25% (ranges between 10%-35%). The bioavailability of the suspension is 1.6 times higher than that of the oral tablet. With the tablet, food decreases the exposure to valsartan by approximately 40% and peak plasma concentration by approximately 50%. AUC and Cmax values of valsartan genereally increase linearly with increasing dose over the therapeutic dose range. Valsartan does not accumulate appreciably in plasma following repetitive administration [FDA label].; ; After one oral dose, the antihypertensive activity of valsartan begins within approximately 2 hours and peaks within 4-6 hours in most patients [F3139].
DESCRIPTION Valsartan is an antagonist with high affinity for the type I (AT1) angiotensin receptor. (GtoPdb)
ABSORPTION Absolute bioavailability for valsartan is approximately 25% (ranges between 10%-35%). The bioavailability of the suspension is 1.6 times higher than that of the oral tablet. With the tablet, food decreases the exposure to valsartan by approximately 40% and peak plasma concentration by approximately 50%. AUC and Cmax values of valsartan genereally increase linearly with increasing dose over the therapeutic dose range. Valsartan does not accumulate appreciably in plasma following repetitive administration [FDA label]. After one oral dose, the antihypertensive activity of valsartan begins within approximately 2 hours and peaks within 4-6 hours in most patients [F3139].
DESCRIPTION Adenosine receptor antagonist (Tocris Bioactive Compound Library)
DESCRIPTION High affinity, selective AT1 antagonist (Tocriscreen Plus)
Cell lines
0
Organisms
1
Compound Sets
28
Axon Medchem Screening Library
3106
Cayman Chemical Bioactives
14178
25226
ChEMBL Approved Drugs
CHEMBL1069
ChEMBL Drugs
CHEMBL1069
Concise Guide to Pharmacology 2017/18
3937
593
Drug Repurposing Hub
DrugBank
DB00177
DrugBank Approved Drugs
DB00177
DrugCentral
2806
DrugCentral Approved Drugs
2806
DrugMAP
DMREUQ6
DrugMAP Approved Drugs
DMREUQ6
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS101792
Guide to Pharmacology
3937
593
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL1069
MedChem Express Bioactive Compound Library
HY-18204
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
80M03YXJ7I
NIH Clinical Collections (NCC)
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Valsartan(Diovan)
TargetMol Bioactive Compound Library
T6716
The Spectrum Collection
Tocris Bioactive Compound Library
4216
Tocriscreen Plus
4216
ZINC Tool Compounds
ZINC000003875259
External IDs
58
Properties
(calculated by RDKit )
Molecular Weight
435.23
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
2
Rotatable Bonds
10
Ring Count
3
Aromatic Ring Count
3
cLogP
4.16
TPSA
112.07
Fraction CSP3
0.38
Chiral centers
1.0
Largest ring
6.0
QED
0.49
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
Endocrinology/Hormones
GPCR/G protein
Target
angiotensin II receptor
AGTR1
AT1 antagonist
Angiotensin Receptor
Primary Target
Angiotensin AT1 Receptors
MOA
Antagonist
angiotensin receptor antagonist
Indication
hypertension, congestive heart failure, congestive heart failure
Therapeutic Indication
Antihypertensive
Therapeutic Class
Cardiovascular
Antihypertensive Agents
Source data