Identification

Name
Losartan
Accession Number
DB00678
Description

Losartan is an angiotensin II receptor blocker (ARB) used to treat hypertension.3 Angiotensin-converting enzyme (ACE) inhibitors are used for a similar indication but are associated with a cough.3 When patients with ACE inhibitor associated coughs are switched to ARBs like losartan, they have an incidence of cough similar to placebo or hydrochlorothiazide.3 Losartan is available as losartan potassium oral tablets as well as a combination tablet of losartan potassium and hydrochlorothiazide.3,4 Patients taking losartan should have their renal function and potassium levels monitored.3 Losartan was granted FDA approval on 14 April 1995.3

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 422.911
Monoisotopic: 422.162187095
Chemical Formula
C22H23ClN6O
Synonyms
  • (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol
  • 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole
  • Losartan
External IDs
  • DUP 89
  • HGP-1405
  • HGP1405
  • MK594

Pharmacology

Indication

Losartan is indicated to treat hypertension in patients older than 6 years, reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (though this benefit may not extend to patients with African heritage), and to treat diabetic nephropathy with elevated serum creatinine and proteinuria in patients with type 2 diabetes and hypertension.3 Losartan with hydrochlorothiazide is indicated to treat hypertension and to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (though this benefit may not extend to patients with African heritage).4

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Losartan is an angiotensin II receptor blocker used to treat hypertension, diabetic nephropathy, and to reduce the risk of stroke.1,3,4 Losartan has a long duration of action as it is given once daily.3,4 Patients taking losartan should be regularly monitored for hypotension, renal function, and potassium levels.3,4

Mechanism of action

Losartan reversibly and competitively prevents angiotensin II binding to the AT1 receptor in tissues like vascular smooth muscle and the adrenal gland.3,4 Losartan and its active metabolite bind the AT1 receptor with 1000 times more affinity than they bind to the AT2 receptor.3,4 The active metabolite of losartan is 10-40 times more potent by weight than unmetabolized losartan as an inhibitor of AT1 and is a non-competitive inhibitor.3,4 Losartan's prevention of angiotensin II binding causes vascular smooth muscle relaxation, lowering blood pressure.3,4

Angiotensin II would otherwise bind to the AT1 receptor and induce vasoconstriction, raising blood pressure.3,4

TargetActionsOrganism
AType-1 angiotensin II receptor
antagonist
Humans
Absorption

Losartan is approximately 33% orally bioavailable.1,3,4 Losartan has a Tmax of 1 hour and the active metabolite has a Tmax of 3-4 hours.1,3,4 Taking losartan with food decreases the Cmax but does only results in a 10% decrease in the AUC of losartan and its active metabolite.1,3,4 A 50-80mg oral dose of losartan leads to a Cmax of 200-250ng/mL.1

Volume of distribution

The volume of distribution of losartan is 34.4±17.9L and 10.3±1.1L for the active metabolite (E-3174).1

Protein binding

Losartan is 98.6-98.8% protein bound and the active metabolite (E-3174) is 99.7% protein bound in serum.1

Metabolism

Losartan is metabolized to an aldehyde intermediate, E-3179, which is further metabolized to a carboxylic acid, E-3174, by cytochrome P450s like CYP2C9.1 Losartan can also be hydroxylated to an inactive metabolite, P1.1 Approximately 14% of losartan is metabolized to E-3174.1 Losartan can be metabolized by CYP3A4, CYP2C9, and CYP2C10.1 Losartan can also be glucuronidated by UGT1A1, UGT1A3, UGT1A10, UGT2B7, and UGT 2B17.2

Hover over products below to view reaction partners

Route of elimination

A single oral dose of losartan leads to 4% recovery in the urine as unchanged losartan, 6% in the urine as the active metabolite.3,4 Oral radiolabelled losartan is 35% recovered in urine and 60% in feces.3,4 Intravenous radiolabelled losartan is 45% recovered in urine and 50% in feces.3,4

Half-life

The terminal elimination half life of losartan is 1.5-2.5 hours while the active metabolite has a half life of 6-9 hours.1

Clearance

Losartan has a total plasma clearance of 600mL/min and a renal clearance of 75mL/min.1 E-3174, the active metabolite, has a total plasma clearance of 50mL/min and a renal clearance of 25mL/min.1

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The oral TDLO in mice is 1000mg/kg and in rats is 2000mg/kg.3,4 In humans the TDLO for men is 10mg/kg/2W and for women is 1mg/kg/1D.5

Symptoms of overdose are likely to include hypotension, tachycardia, or bradycardia due to vagal stimulation.3,4 Supportive treatment should be instituted for symptomatic hypotension.3,4 Hemodialysis will not remove losartan or its active metabolite due to their high rates of protein binding.3,4

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Losartan Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Losartan can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Losartan can be increased when combined with Abatacept.
AbirateroneThe metabolism of Losartan can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Losartan.
AcebutololLosartan may increase the arrhythmogenic activities of Acebutolol.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Losartan is combined with Aceclofenac.
AcemetacinThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Losartan is combined with Acemetacin.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Losartan.
AcetohexamideThe metabolism of Losartan can be decreased when combined with Acetohexamide.
Acetyl sulfisoxazoleThe metabolism of Losartan can be decreased when combined with Acetyl sulfisoxazole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take at the same time every day.
  • Take with or without food. Food delays absorption, but does not affect the extent of absorption.

Products

Product Ingredients
IngredientUNIICASInChI Key
Losartan potassium3ST302B24A124750-99-8OXCMYAYHXIHQOA-UHFFFAOYSA-N
Product Images
International/Other Brands
Lortaan
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act LosartanTabletOralActavis Pharma Company2012-01-252019-08-07Canada flag
Act LosartanTabletOralActavis Pharma Company2012-01-252019-08-07Canada flag
Act LosartanTabletOralActavis Pharma Company2012-01-252019-08-07Canada flag
CozaarTablet, film coated50 mg/1OralPhysicians Total Care, Inc.1996-04-01Not applicableUS flag00006 0952 54 nlmimage10 c51362fb
CozaarTablet, film coated25 mg/1OralMerck Sharp & Dohme Corp.1995-04-14Not applicableUS flag
CozaarTablet25 mgOralMerck Ltd.1995-12-31Not applicableCanada flag
CozaarTablet, film coated25 mg/1OralRemedy Repack2011-05-192011-05-20US flag
CozaarTablet, film coated100 mg/1OralMerck Sharp & Dohme Corp.1995-04-14Not applicableUS flag0006 096020180810 16125 18fhek0
CozaarTablet, film coated50 mg/1OralMed Pharma Co., Ltd.1995-04-142012-07-11US flag
CozaarTablet, film coated100 mg/1Oralbryant ranch prepack1995-04-142009-10-01US flag63629 291220180907 15195 ry6v4m
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ag-losartanTabletOralAngita Pharma Inc.2018-06-27Not applicableCanada flag
Ag-losartanTabletOralAngita Pharma Inc.2018-06-27Not applicableCanada flag
Ag-losartanTabletOralAngita Pharma Inc.2018-06-27Not applicableCanada flag
Apo-losartanTabletOralApotex Corporation2012-01-25Not applicableCanada flag
Apo-losartanTabletOralApotex Corporation2012-04-13Not applicableCanada flag
Apo-losartanTabletOralApotex Corporation2012-01-25Not applicableCanada flag
Auro-losartanTabletOralAuro Pharma Inc2013-03-26Not applicableCanada flag
Auro-losartanTabletOralAuro Pharma Inc2013-03-26Not applicableCanada flag
Auro-losartanTabletOralAuro Pharma Inc2013-03-26Not applicableCanada flag
Bio-losartanTabletOralBiomed Pharma2016-05-09Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Act Losartan/hctLosartan potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralActavis Pharma Company2012-07-032018-06-25Canada flag
Act Losartan/hctLosartan potassium (100 mg) + Hydrochlorothiazide (12.5 mg)TabletOralActavis Pharma Company2012-07-032018-06-25Canada flag
Act Losartan/hctLosartan potassium (50 mg) + Hydrochlorothiazide (12.5 mg)TabletOralActavis Pharma Company2012-07-032018-06-25Canada flag
Ag-losartan HctzLosartan potassium (50 mg) + Hydrochlorothiazide (12.5 mg)TabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Ag-losartan HctzLosartan potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Apo-losartan/hctzLosartan potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralApotex Corporation2012-01-25Not applicableCanada flag
Apo-losartan/hctzLosartan potassium (100 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex Corporation2012-01-25Not applicableCanada flag
Apo-losartan/hctzLosartan potassium (50 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex Corporation2012-01-25Not applicableCanada flag
Auro-losartan HCTLosartan potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralAuro Pharma Inc2014-04-29Not applicableCanada flag
Auro-losartan HCTLosartan potassium (100 mg) + Hydrochlorothiazide (12.5 mg)TabletOralAuro Pharma Inc2014-04-29Not applicableCanada flag

Categories

ATC Codes
C09CA01 — LosartanC09DA01 — Losartan and diureticsC09DB06 — Losartan and amlodipine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as biphenyls and derivatives. These are organic compounds containing to benzene rings linked together by a C-C bond.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Biphenyls and derivatives
Direct Parent
Biphenyls and derivatives
Alternative Parents
Phenyltetrazoles and derivatives / 1,2,4,5-tetrasubstituted imidazoles / N-substituted imidazoles / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Primary alcohols / Organopnictogen compounds / Organonitrogen compounds / Organochlorides
show 2 more
Substituents
1,2,4,5-tetrasubstituted imidazole / Alcohol / Aromatic alcohol / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Biphenyl / Heteroaromatic compound
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, biphenylyltetrazole (CHEBI:6541)

Chemical Identifiers

UNII
JMS50MPO89
CAS number
114798-26-4
InChI Key
PSIFNNKUMBGKDQ-UHFFFAOYSA-N
InChI
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)
IUPAC Name
[2-butyl-4-chloro-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazol-5-yl]methanol
SMILES
CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NNN=N1

References

Synthesis Reference

Gordon C. Campbell, Jr., Anil M. Dwivedi, Dorothy A. Levorse, James A. McCauley, Krishnaswamy S. Raghavan, "Polymorphs of losartan and the process for the preparation of form II of losartan." U.S. Patent US5608075, issued May, 1994.

US5608075
General References
  1. Sica DA, Gehr TW, Ghosh S: Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814. [PubMed:16029066]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  3. FDA Approved Drug Products: Losartan Oral Tablets [Link]
  4. FDA Approved Drug Products: Losartan and Hydrochlorothiazide Oral Tablets [Link]
  5. Cayman Chemicals: Losartan Potassium MSDS [Link]
Human Metabolome Database
HMDB0014816
KEGG Drug
D08146
KEGG Compound
C07072
PubChem Compound
3961
PubChem Substance
46506538
ChemSpider
3824
BindingDB
82258
RxNav
52175
ChEBI
6541
ChEMBL
CHEMBL191
ZINC
ZINC000003873160
Therapeutic Targets Database
DAP000523
PharmGKB
PA450268
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
LSN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Losartan
AHFS Codes
  • 24:32.08 — Angiotensin Ii Receptor Antagonists
PDB Entries
5x23 / 5x24 / 5xxi / 6vlt
FDA label
Download (212 KB)
MSDS
Download (19 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentBipolar Disorder (BD) / Cardiovascular Heart Disease / Major Depressive Disorder (MDD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenia / Serious Mental Illness1
4Active Not RecruitingTreatmentEmphysema1
4CompletedNot AvailableHigh Blood Pressure (Hypertension)1
4CompletedBasic ScienceChemoreceptor Apnea / Hypoxia / Respiration; Sleep Disorder / Sleep Disordered Breathing (SDB)1
4CompletedBasic ScienceRejection, Transplant1
4CompletedDiagnosticHyperaldosteronism1
4CompletedOtherBMI >30 kg/m2 / High Blood Pressure (Hypertension) / Hyperglycemia1
4CompletedPreventionKidney Diseases / Proteinuria1
4CompletedPreventionKidney Stones1
4CompletedPreventionNephropathy, Diabetic1

Pharmacoeconomics

Manufacturers
  • Merck research laboratories div merck co inc
  • Teva pharmaceuticals usa inc
  • Merck & Co., Inc.
Packagers
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • Dispensing Solutions
  • Ipca Laboratories Ltd.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Merck & Co.
  • Mylan
  • Neuman Distributors Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepak Systems Inc.
  • Remedy Repack
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Torrent Pharmaceuticals
  • Vangard Labs Inc.
Dosage Forms
FormRouteStrength
Capsule, coatedOral5 mg
Capsule, coatedOral2.5 mg
Tablet, film coated50 mg
Tablet, film coated100 mg
Tablet, coatedOral100 mg
Tablet, coatedOral12.5 mg
Tablet, film coatedOral50 MG
Tablet, film coatedOral
TabletOral25 mg
Tablet, film coatedOral100 MG
Tablet, film coatedOral12.5 MG
Tablet, film coatedOral25 MG
Tablet, coatedOral5 mg
Tablet, film coatedOral75 MG
TabletOral100 mg
TabletOral50 mg
Tablet, coatedOral25 mg
TabletOral100 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral50 mg/1
TabletOral
Tablet, film coatedOral
Tablet
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Powder, for suspensionOral2.5 MG/ML
TabletOral
Tablet, film coated25 mg
Tablet, coatedOral50 mg
TabletOral12.5 mg
Prices
Unit descriptionCostUnit
Losartan Potassium 90 50 mg tablet Bottle211.78USD bottle
Losartan Potassium-HCTZ 30 50-12.5 mg tablet Bottle78.05USD bottle
Hyzaar 100-25 mg tablet3.91USD tablet
Hyzaar 100-12.5 mg tablet3.87USD tablet
Hyzaar 100-12.5 tablet3.61USD tablet
Hyzaar 100-25 tablet3.61USD tablet
Losartan Potassium-HCTZ 100-12.5 mg tablet3.54USD tablet
Losartan Potassium-HCTZ 100-25 mg tablet3.54USD tablet
Cozaar 100 mg tablet3.41USD tablet
Losartan potassium 100 mg tablet3.14USD tablet
Hyzaar 50-12.5 mg tablet2.97USD tablet
Hyzaar 50-12.5 tablet2.65USD tablet
Cozaar 50 mg tablet2.5USD tablet
Losartan potassium 50 mg tablet2.26USD tablet
Cozaar 25 mg tablet1.92USD tablet
Losartan potassium 25 mg tablet1.72USD tablet
Cozaar 100 mg Tablet1.31USD tablet
Cozaar 25 mg Tablet1.31USD tablet
Cozaar 50 mg Tablet1.31USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5210079No1993-05-112010-11-11US flag
US5608075No1997-03-042009-03-04US flag
CA2085584No2003-02-112011-06-07Canada flag
CA1334092No1995-01-242012-01-24Canada flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178-184http://www.chemspider.com/Chemical-Structure.3824.html
boiling point (°C)682http://www.chemspider.com/Chemical-Structure.3824.html
water solubility<1mg/mLhttp://www.chemspider.com/Chemical-Structure.3824.html
logP1.19https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/20-386S019_Cozaar_EAFONSI.pdf
pKa5.5MERCK INDEX (1996); approx.
Predicted Properties
PropertyValueSource
Water Solubility0.0047 mg/mLALOGPS
logP4.5ALOGPS
logP5.08ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)7.4ChemAxon
pKa (Strongest Basic)4.12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.51 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity131.85 m3·mol-1ChemAxon
Polarizability44.86 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier-0.7812
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.6993
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IIInhibitor0.5309
Renal organic cation transporterNon-inhibitor0.5689
CYP450 2C9 substrateNon-substrate0.6839
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.6226
CYP450 1A2 substrateInhibitor0.5514
CYP450 2C9 inhibitorNon-inhibitor0.5423
CYP450 2D6 inhibitorNon-inhibitor0.8102
CYP450 2C19 inhibitorInhibitor0.6288
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7049
Ames testNon AMES toxic0.5382
CarcinogenicityNon-carcinogens0.6595
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6055 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5781
hERG inhibition (predictor II)Inhibitor0.8084
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0000900000-657db16bb4bfe9184114
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-056r-0900000000-43bb8508cd1dbc71bcee
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0900000000-55368087829d113fdb7b
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0900000000-af470646c547613f82a0
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0900000000-746dcf7a43a3f8839c1d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0900000000-0bee80f7ccbc4b68eee0
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-0900000000-d845ae166a10faff242a
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-2900000000-d39a309c02e1aaa956b0
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-7900000000-d27d10ab008deb157e7a
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00fr-0900700000-fef78a7f52d4aa515bb4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00fr-0900600000-c62f0db44e17f79e0c70
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0034900000-22ba49ec64d374c8965e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0191000000-8ff1b5a21f6ef4a462cd
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0590000000-9841ff7f881c3e9c11b9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a59-0960000000-a24e287a018dae01dd0d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a5c-0930000000-ff3e675bd445225bf04e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0pxu-0920000000-9adf4aef59fc1545fea6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0v00-1900000000-3591888cf5831cbe3d11
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0wmi-2900000000-ab9304c8cebc201d0178
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0j70-5900000000-efa87b7770206ac0ff3e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0491300000-f4b08850a154cfc2117c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0591300000-32a922edf20b3eb76950

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name
AGTR1
Uniprot ID
P30556
Uniprot Name
Type-1 angiotensin II receptor
Molecular Weight
41060.53 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Sardo MA, Castaldo M, Cinquegrani M, Bonaiuto M, Fontana L, Campo S, Campo GM, Altavilla D, Saitta A: Effects of AT1 receptor antagonist losartan on sICAM-1 and TNF-alpha levels in uncomplicated hypertensive patients. Angiology. 2004 Mar-Apr;55(2):195-203. [PubMed:15026875]
  3. Dickstein K, Timmermans P, Segal R: Losartan: a selective angiotensin II type 1 (AT1) receptor antagonist for the treatment of heart failure. Expert Opin Investig Drugs. 1998 Nov;7(11):1897-914. [PubMed:15991937]
  4. Anand-Srivastava MB, Palaparti A: Angiotensin-II-induced enhanced expression of Gi proteins is attenuated by losartan in A10 vascular smooth muscle cells: role of AT1 receptors. Can J Physiol Pharmacol. 2003 Feb;81(2):150-8. [PubMed:12710529]
  5. Rocha I, Bras-Rosario L, Amparo-Barros M, Silva-Carvalho L: Angiotensin AT1 receptor antagonist losartan and the defence reaction in the anaesthetised rat. Effect on the carotid chemoreflex. Exp Physiol. 2003 May;88(3):309-14. [PubMed:12719755]
  6. Guan J, Cheng DY, Chen XJ, Zhang Y, Wang H, Su QL: [The effects of losartan on pulmonary arterial collagen and AT1 in chronic hypoxic rats]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2004 Nov;35(6):774-7. [PubMed:15573751]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Song JC, White CM: Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. Pharmacotherapy. 2000 Feb;20(2):130-9. [PubMed:10678291]
  2. Sica DA, Gehr TW, Ghosh S: Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814. [PubMed:16029066]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  4. Yasar U, Forslund-Bergengren C, Tybring G, Dorado P, Llerena A, Sjoqvist F, Eliasson E, Dahl ML: Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther. 2002 Jan;71(1):89-98. [PubMed:11823761]
  5. Flockhart Table of Drug Interactions [Link]
  6. FDA label Losartan [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Song JC, White CM: Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. Pharmacotherapy. 2000 Feb;20(2):130-9. [PubMed:10678291]
  2. Sica DA, Gehr TW, Ghosh S: Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814. [PubMed:16029066]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  4. Mukai Y, Senda A, Toda T, Hayakawa T, Eliasson E, Rane A, Inotsume N: Drug-drug Interaction between Losartan and Paclitaxel in Human Liver Microsomes with Different CYP2C8 Genotypes. Basic Clin Pharmacol Toxicol. 2015 Jun;116(6):493-8. doi: 10.1111/bcpt.12355. Epub 2014 Dec 23. [PubMed:25424246]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
The current evidence available for this enzyme inhibition is limited to one in vitro study.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Taavitsainen P, Kiukaanniemi K, Pelkonen O: In vitro inhibition screening of human hepatic P450 enzymes by five angiotensin-II receptor antagonists. Eur J Clin Pharmacol. 2000 May;56(2):135-40. [PubMed:10877007]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein kinase c binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The major substrates of this isozyme are eugenol > 4-methylumbe...
Gene Name
UGT2B17
Uniprot ID
O75795
Uniprot Name
UDP-glucuronosyltransferase 2B17
Molecular Weight
61094.915 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Mukai Y, Senda A, Toda T, Hayakawa T, Eliasson E, Rane A, Inotsume N: Drug-drug Interaction between Losartan and Paclitaxel in Human Liver Microsomes with Different CYP2C8 Genotypes. Basic Clin Pharmacol Toxicol. 2015 Jun;116(6):493-8. doi: 10.1111/bcpt.12355. Epub 2014 Dec 23. [PubMed:25424246]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Sica DA, Gehr TW, Ghosh S: Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814. [PubMed:16029066]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [PubMed:11895100]
  2. Borgnia MJ, Eytan GD, Assaraf YG: Competition of hydrophobic peptides, cytotoxic drugs, and chemosensitizers on a common P-glycoprotein pharmacophore as revealed by its ATPase activity. J Biol Chem. 1996 Feb 9;271(6):3163-71. [PubMed:8621716]
  3. Soldner A, Benet LZ, Mutschler E, Christians U: Active transport of the angiotensin-II antagonist losartan and its main metabolite EXP 3174 across MDCK-MDR1 and caco-2 cell monolayers. Br J Pharmacol. 2000 Mar;129(6):1235-43. [PubMed:10725273]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. [PubMed:10049739]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Urate transmembrane transporter activity
Specific Function
Required for efficient urate re-absorption in the kidney. Regulates blood urate levels. Mediates saturable urate uptake by facilitating the exchange of urate against organic anions.
Gene Name
SLC22A12
Uniprot ID
Q96S37
Uniprot Name
Solute carrier family 22 member 12
Molecular Weight
59629.57 Da
References
  1. Lipkowitz MS: Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep. 2012 Apr;14(2):179-88. doi: 10.1007/s11926-012-0240-z. [PubMed:22359229]
  2. Burnier M, Roch-Ramel F, Brunner HR: Renal effects of angiotensin II receptor blockade in normotensive subjects. Kidney Int. 1996 Jun;49(6):1787-90. [PubMed:8743498]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sugar:proton symporter activity
Specific Function
Transport urate and fructose. May have a role in the urate reabsorption by proximal tubules. Also transports glucose at low rate.
Gene Name
SLC2A9
Uniprot ID
Q9NRM0
Uniprot Name
Solute carrier family 2, facilitated glucose transporter member 9
Molecular Weight
58701.205 Da
References
  1. Lipkowitz MS: Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep. 2012 Apr;14(2):179-88. doi: 10.1007/s11926-012-0240-z. [PubMed:22359229]
  2. Burnier M, Roch-Ramel F, Brunner HR: Renal effects of angiotensin II receptor blockade in normotensive subjects. Kidney Int. 1996 Jun;49(6):1787-90. [PubMed:8743498]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55

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