Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H23ClN6O |
Molecular Weight | 422.911 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCC1=NC(Cl)=C(CO)N1CC2=CC=C(C=C2)C3=C(C=CC=C3)C4=NN=NN4
InChI
InChIKey=PSIFNNKUMBGKDQ-UHFFFAOYSA-N
InChI=1S/C22H23ClN6O/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,(H,25,26,27,28)
Molecular Formula | C22H23ClN6O |
Molecular Weight | 422.911 |
Charge | 0 |
Count |
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Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.drugs.com/monograph/cozaar.html
Sources: https://www.drugs.com/monograph/cozaar.html
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.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2094256 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16610806 |
4.0 nM [Kd] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | COZAAR Approved UseAngiotensin 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 Date7.9781757E11 |
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Preventing | COZAAR Approved UsePreliminary 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 Date7.9781757E11 |
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Primary | COZAAR Approved UseManagement 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 Date7.9781757E11 |
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Primary | COZAAR Approved UseAngiotensin 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 Date7.9781757E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0 |
moderate [IC50 138 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0 |
slight | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0 |
weak [IC50 210 uM] | |||
yes [IC50 1.5 uM] | ||||
yes [IC50 1.6 uM] | ||||
yes [IC50 12 uM] | ||||
yes [IC50 18 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0 |
yes [IC50 524 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10877007/ Page: 137.0 |
yes [IC50 81 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/20222053/ Page: 6.0 |
yes [IC50 >100 uM] | |||
yes [Ki 24 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
minor | ||||
minor | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2,8 |
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; Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2,8 |
||
Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2.0 |
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%; Sources: https://pubmed.ncbi.nlm.nih.gov/16029066/ Page: 2.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/10715269/ Page: 4.0 |
PubMed
Title | Date | PubMed |
---|---|---|
The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure. | 1999 |
|
Angioedema due to losartan. | 1999 Sep |
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Losartan-induced angioedema. | 1999 Sep |
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Randomised comparison of losartan vs. captopril on quality of life in elderly patients with symptomatic heart failure: the losartan heart failure ELITE quality of life substudy. | 2000 |
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Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients. | 2000 Sep |
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Intrarenal renin-angiotensin system contributes to tubular acidification adaptation following uninephrectomy. | 2001 |
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Tonic suppression of spontaneous baroreceptor reflex by endogenous angiotensins via AT(2) subtype receptors at nucleus reticularis ventrolateralis in the rat. | 2001 Apr |
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Atypical angiotensin receptors may mediate water intake induced by central injections of angiotensin II and of serotonin in pigeons. | 2001 Apr 20 |
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Left ventricular hypertrophy and angiotensin II antagonists. | 2001 Feb |
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Angiotensin II increases vesicular trafficking in brain neurons. | 2001 Feb |
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Expression of cell cycle proteins in blood vessels of angiotensin II-infused rats: role of AT(1) receptors. | 2001 Feb |
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Role of endothelin and isoprostanes in slow pressor responses to angiotensin II. | 2001 Feb |
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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 |
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Combined therapy with an angiotensin II receptor blocker and an angiotensin-converting enzyme inhibitor in heart failure. | 2001 Feb |
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Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin II type 1 receptor blockade. | 2001 Feb |
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Angiotensin II is involved in nitric oxide synthase and cyclo-oxygenase inhibition-induced leukocyte-endothelial cell interactions in vivo. | 2001 Feb |
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Hyperoxia/normoxia-driven retinal angiogenesis in mice: a role for angiotensin II. | 2001 Feb |
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Acute administration of nicotine impairs the hypotensive responses to bradykinin in rats. | 2001 Feb 16 |
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Pressure overload increases GATA4 binding activity via endothelin-1. | 2001 Feb 6 |
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Losartan versus enalapril on cerebral edema and proteinuria in stroke-prone hypertensive rats. | 2001 Jan |
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New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure. | 2001 Jan |
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Interaction between paracrine tumor necrosis factor-alpha and paracrine angiotensin II during myocardial ischemia. | 2001 Jan |
|
Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan. | 2001 Jan 16 |
|
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 |
|
The role of angiotensin receptor blockers in the management of chronic heart failure. | 2001 Mar 12 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/monograph/cozaar.html
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16610806
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
Edited
Fri Dec 16 18:01:28 UTC 2022
by
admin
on
Fri Dec 16 18:01:28 UTC 2022
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Record UNII |
JMS50MPO89
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Record Status |
Validated (UNII)
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Record Version |
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-
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000000070
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FDA ORPHAN DRUG |
357211
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LIVERTOX |
NBK547842
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NCI_THESAURUS |
C66930
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WHO-ATC |
C09DA01
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WHO-VATC |
QC09DA01
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NDF-RT |
N0000175561
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WHO-VATC |
QC09DB06
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WHO-ATC |
C09CA01
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FDA ORPHAN DRUG |
668618
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EU-Orphan Drug |
EU/3/19/2142
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WHO-VATC |
QC09CA01
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WHO-ATC |
C09DB06
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Code System | Code | Type | Description | ||
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52175
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PRIMARY | RxNorm | ||
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JMS50MPO89
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PRIMARY | |||
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7043
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PRIMARY | |||
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6541
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PRIMARY | |||
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114798-26-4
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PRIMARY | |||
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1610
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PRIMARY | |||
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LOSARTAN
Created by
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PRIMARY | |||
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DB00678
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PRIMARY | |||
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590
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PRIMARY | |||
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CHEMBL191
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SUB32953
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ALTERNATIVE | |||
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Losartan
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PRIMARY | |||
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SUB08593MIG
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PRIMARY | |||
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149504
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PRIMARY | |||
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JMS50MPO89
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PRIMARY | |||
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C66869
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PRIMARY | |||
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758699
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PRIMARY | |||
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DTXSID7023227
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PRIMARY | |||
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6913
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PRIMARY | |||
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M6911
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PRIMARY | Merck Index | ||
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D019808
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PRIMARY | |||
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3961
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PRIMARY |
Related Record | Type | Details | ||
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DERIVATIVE -> PARENT | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> INHIBITOR |
IC50
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METABOLIC ENZYME -> INHIBITOR |
Liver concentrations were estimated to be about 50 micromolar. this indicates that Losartan might inhibit the AA metabolism in the liver.
IC50
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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TRANSPORTER -> INHIBITOR |
Related Record | Type | Details | ||
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METABOLITE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
Related Record | Type | Details | ||
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IMPURITY -> PARENT |
NMBA is a priority toxic pollutant. FDA is temporarily not objecting to Losartan with NMBA below 9.82 ppm remaining on the market.
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IMPURITY -> PARENT |
Acceptable intake level of NDEA in ppm.
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IMPURITY GENOTOXIC->PARENT |
NDMA is an organic chemical that is part of 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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Biological Half-life | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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Elimination PHARMACOKINETIC |
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