U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C22H22ClN6O.K
Molecular Weight 461.0017
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOSARTAN POTASSIUM

SMILES

CCCCc1nc(c(CO)n1Cc2ccc(cc2)-c3ccccc3C4=NN=[N-]=N4)Cl.[K+]

InChI

InChIKey=OXCMYAYHXIHQOA-UHFFFAOYSA-N
InChI=1S/C22H22ClN6O.K/c1-2-3-8-20-24-21(23)19(14-30)29(20)13-15-9-11-16(12-10-15)17-6-4-5-7-18(17)22-25-27-28-26-22;/h4-7,9-12,30H,2-3,8,13-14H2,1H3;/q-1;+1

HIDE SMILES / InChI

Molecular Formula C22H22ClN6O
Molecular Weight 421.9034
Charge -1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula K
Molecular Weight 39.0983
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Losartan is a selective, competitive angiotensin II receptor type 1 (AT1) antagonist. Losartant is recommended as one of several preferred agents for the initial management of hypertension. Administration of losartan reduces the risk of stroke in patients with hypertension and left ventricular hypertrophy. Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria in patients with type 2 diabetes and a history of hypertension.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.0 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
COZAAR

Approved Use

Angiotensin II receptor antagonists are recommended as one of several preferred agents for the initial management of hypertension; other options include ACE inhibitors, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes. Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

Launch Date

7.9781757E11
Preventing
COZAAR

Approved Use

Preliminary evidence suggests that aspirin therapy at baseline in patients receiving losartan may reduce the risk of combined cardiovascular death, stroke, and acute MI compared with aspirin therapy at baseline in patients receiving atenolol, but there is evidence that this benefit does not apply to Black patients.

Launch Date

7.9781757E11
Primary
COZAAR

Approved Use

Management of diabetic nephropathy manifested by elevated Scr and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes mellitus and hypertension.

Launch Date

7.9781757E11
Primary
COZAAR

Approved Use

Angiotensin II receptor antagonists are considered a reasonable alternative for inhibition of the renin-angiotensin system in patients with heart failure and reduced left ventricular ejection fraction (LVEF) who are intolerant of ACE inhibitors; because of their established benefits, ACE inhibitors are preferred.

Launch Date

7.9781757E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
224 ng/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
442 ng × h/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.1 h
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1.3%
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LOSARTAN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
minor
minor
minor
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: coadministration with fluconazole (CYP2C9 inhibitor) increased AUC24 by 66%; coadministration with phenytoin (CYP2C9 inducer) increased AUC24 of drug by 17% and 29% in those with CYP2C9*1/*1 genotype;
Page: 2,8
yes
yes (co-administration study)
Comment: coadministration with ketoconazole or erythromycin (CYP3A4 inhibitors) had no effect on AUC24 of drug; coadministration with rifampin (CYP3A4 inducer) increased AUC24 of drug by 35%;
Page: 2.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Effects of losartan on ventricular remodeling in experimental infarction in rats.
2000 Dec
[Acute kidney failure and losartan: a recently observed event of antagonists of angiotensin II AT1 receptors].
2000 Sep
The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure.
2001 Apr
Angiotensin II stimulates cardiac L-type Ca(2+) current by a Ca(2+)- and protein kinase C-dependent mechanism.
2001 Apr
Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat.
2001 Apr
Atypical angiotensin receptors may mediate water intake induced by central injections of angiotensin II and of serotonin in pigeons.
2001 Apr 20
Left ventricular hypertrophy and angiotensin II antagonists.
2001 Feb
Angiotensin II increases vesicular trafficking in brain neurons.
2001 Feb
Expression of cell cycle proteins in blood vessels of angiotensin II-infused rats: role of AT(1) receptors.
2001 Feb
Angiotensin II induces migration and Pyk2/paxillin phosphorylation of human monocytes.
2001 Feb
Role of endothelin and isoprostanes in slow pressor responses to angiotensin II.
2001 Feb
Angiotensin II relaxes microvessels via the AT(2) receptor and Ca(2+)-activated K(+) (BK(Ca)) channels.
2001 Feb
Mortality after coronary artery occlusion in different models of cardiac hypertrophy in rats.
2001 Feb
Role of angiotensin II in altered baroreflex function of conscious rabbits during late pregnancy.
2001 Feb
Modulation of alveolar-capillary sodium handling as a mechanism of protection of gas transfer by enalapril, and not by losartan, in chronic heart failure.
2001 Feb
Combined therapy with an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor in heart failure.
2001 Feb
DNA damage of lymphocytes in experimental chronic renal failure: beneficial effects of losartan.
2001 Feb
Different effects of angiotensin II and catecholamine on renal cell apoptosis and proliferation in rats.
2001 Feb
A two-state receptor model for the interaction between angiotensin II type 1 receptors and non-peptide antagonists.
2001 Feb 1
Angiotensin II type 1 receptor blockers.
2001 Feb 13
Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase.
2001 Feb 13
Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy.
2001 Feb 13
Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats.
2001 Feb 16
Losartan and fetal toxic effects.
2001 Feb 3
[Well tolerated sartans. More normal blood pressure finally?].
2001 Feb 8
[Treating not only blood pressure. Advantages for microcirculation].
2001 Feb 8
Acute effects of E-3174, a human active metabolite of losartan, on the cardiovascular system in tachycardia-induced canine heart failure.
2001 Jan
Role of the central nervous system in the development of hypertension produced by chronic nitric oxide blockade in rats.
2001 Jan
Contribution of angiotensin II, endothelin 1 and the endothelium to the slow inotropic response to stretch in ferret papillary muscle.
2001 Jan
Functional expression of angiotensin II receptors in type-I cells of the rat carotid body.
2001 Jan
Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats.
2001 Jan
Relation of left ventricular geometry and function to systemic hemodynamics in hypertension: the LIFE Study. Losartan Intervention For Endpoint Reduction in Hypertension Study.
2001 Jan
New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure.
2001 Jan
Renal and vascular injury induced by exogenous angiotensin II is AT1 receptor-dependent.
2001 Jan
Angiotensin II inhibits rat arterial KATP channels by inhibiting steady-state protein kinase A activity and activating protein kinase Ce.
2001 Jan 15
Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.
2001 Jan 16
Central interactions between angiotensin II and PGD(2) in the regulation of vasopressin and oxytocin secretion in dehydrated rats.
2001 Jan 19
Mannitol-induced toxicity in a diabetic patient receiving losartan.
2001 Mar
Restoration of normal ventricular electrophysiology in renovascular hypertensive rabbits after treatment with losartan.
2001 Mar
Effect of angiotensin II on venodilator response to nitroglycerin.
2001 Mar
MK-954 (losartan potassium) exerts endothelial protective effects against reperfusion injury: evidence of an e-NOS mRNA overexpression after global ischemia.
2001 Mar
Identification, distribution, and expression of angiotensin II receptors in the normal human prostate and benign prostatic hyperplasia.
2001 Mar
AT(1) receptor blockers prevent sympathetic hyperactivity and hypertension by chronic ouabain and hypertonic saline.
2001 Mar
Effect of oral contraceptives on the renin angiotensin system and renal function.
2001 Mar
Cerebral Na concentration, Na appetite and thirst of sheep: influence of somatostatin and losartan.
2001 Mar
Glucocorticoid modulation of cardiovascular and autonomic function in preterm lambs: role of ANG II.
2001 Mar
Are angiotensin II receptor blockers more efficacious than placebo in heart failure? Implications of ELITE-2. Evaluation of Losartan In The Elderly.
2001 Mar 1
Effect of losartan on degree of mitral regurgitation quantified by echocardiography.
2001 Mar 1
The role of angiotensin receptor blockers in the management of chronic heart failure.
2001 Mar 12
Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis.
2001 Mar 6
Patents

Sample Use Guides

For treatment of hypertension, Joint National Committee (JNC) 8 expert panel recommends initial dosage of 50 mg daily and target dosage of 100 mg daily (given in 1 dose or 2 divided doses) based on dosages used in randomized controlled studies.
Route of Administration: Oral
From 30 to 40 min after confirmation of endothelium removal, the test compounds were incubated at a concentration of 0.1 uM. After an incubation period of 20 or 60 min, aortic preparations were treated with AII, using 3-fold increasing concentrations from 0.1 nM to 1 uM. Kb for binding with angiotensin receptor was 4 nM with 20 min incubation, and 9 nM with 60 min incubation.
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:56:41 UTC 2021
Edited
by admin
on Fri Jun 25 20:56:41 UTC 2021
Record UNII
3ST302B24A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOSARTAN POTASSIUM
EP   HSDB   JAN   MART.   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
TANCIN
Common Name English
LOSARTAN POTASSIUM [EP MONOGRAPH]
Common Name English
LOSARTAN MONOPOTASSIUM SALT
MI  
Common Name English
LOSATA
Common Name English
LOSACAR
Common Name English
HYZAAR COMPONENT LOSARTAN POTASSIUM
Common Name English
LOSARTAN POTASSIUM [USP MONOGRAPH]
Common Name English
LOSARTAN POTASSIUM [VANDF]
Common Name English
COZAAR
Brand Name English
LOSARTAN POTASSIUM [JAN]
Common Name English
NU-LOTAN
Common Name English
DUP 753
Code English
LOSARTAN POTASSIUM [USAN]
Common Name English
LOSARTAN POTASSIUM [ORANGE BOOK]
Common Name English
LOSARTAN POTASSIUM [HSDB]
Common Name English
LOSARTAN MONOPOTASSIUM SALT [MI]
Common Name English
LOSARTAN POTASSIUM [MART.]
Common Name English
MK0954
Code English
ARADOIS
Common Name English
L-158086
Code English
2-BUTYL-4-CHLORO-1-(P-(O-1H-TETRAZOL-5-YLPHENYL)BENZYL)IMIDAZOLE-5-METHANOL, MONOPOTASSIUM SALT
Common Name English
1H-IMIDAZOLE-5-METHANOL, 2-BUTYL-4-CHLORO-1-((2'-(1H-TETRAZOL-5-YL)(1,1'-BIPHENYL)-4-YL)METHYL)-, MONOPOTASSIUM SALT
Common Name English
MK-0954
Code English
ZAART
Common Name English
LOSARTAN POTASSIUM [USP-RS]
Common Name English
DU PONT-753
Code English
E-3340
Code English
LOSARTAN POTASSIUM COMPONENT OF HYZAAR
Common Name English
DUP-753
Code English
PRESARTAN-50
Common Name English
LOSARTAN POTASSIUM [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C66930
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL191
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
PUBCHEM
11476710
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
EVMPD
SUB02974MIG
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
NCI_THESAURUS
C29165
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
CAS
124750-99-8
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
EPA CompTox
124750-99-8
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
RXCUI
203160
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY RxNorm
DRUG BANK
DBSALT000112
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
MERCK INDEX
M6911
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY Merck Index
USP_CATALOG
1370462
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY USP-RS
FDA UNII
3ST302B24A
Created by admin on Fri Jun 25 20:56:41 UTC 2021 , Edited by admin on Fri Jun 25 20:56:41 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY GENOTOXIC->PARENT
Losartan potassium tablets made by Hetero Labs and distributed by Camber Pharmaceuticals contain the impurity, N-Nitroso-N-methyl-4-aminobutyric acid (NMBA), which is a known animal and potential human carcinogen.
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY