Identification

Name
Losartan
Accession Number
DB00678  (APRD00052)
Type
Small Molecule
Groups
Approved
Description

Losartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. Losartan and its longer acting metabolite, E-3174, lower blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); they compete with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Losartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of systolic dysfunction, myocardial infarction, coronary artery disease, and heart failure.

Structure
Thumb
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
  • DuP 89
  • Losartan
External IDs
HGP-1405 / HGP1405 / MK594
Product Ingredients
IngredientUNIICASInChI Key
Losartan Potassium3ST302B24A124750-99-8OXCMYAYHXIHQOA-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act LosartanTablet100 mgOralActavis Pharma Company2012-01-25Not applicableCanada
Act LosartanTablet50 mgOralActavis Pharma Company2012-01-25Not applicableCanada
Act LosartanTablet25 mgOralActavis Pharma Company2012-01-25Not applicableCanada
CozaarTablet, film coated50 mg/1Oralbryant ranch prepack1995-04-14Not applicableUs63629 133720180907 15195 10kqq0
CozaarTablet25 mgOralMerck Ltd.1995-12-31Not applicableCanada
CozaarTablet, film coated50 mg/1OralPhysicians Total Care, Inc.1996-04-01Not applicableUs00006 0952 54 nlmimage10 c51362fb
CozaarTablet, film coated100 mg/1OralMed Pharma Co., Ltd.1995-04-142012-07-11Us
CozaarTablet, film coated100 mg/1OralMerck Sharp & Dohme Limited1995-04-14Not applicableUs0006 096020180810 16125 18fhek0
CozaarTablet, film coated50 mg/1OralCardinal Health1995-04-14Not applicableUs55154 501620180907 15195 3d0psx
CozaarTablet25 mg/1OralRemedy Repack2011-04-072011-04-08Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ag-losartanTablet50 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-losartanTablet25 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-losartanTablet100 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Apo-losartanTablet50 mgOralApotex Corporation2012-01-25Not applicableCanada
Apo-losartanTablet25 mgOralApotex Corporation2012-04-13Not applicableCanada
Apo-losartanTablet100 mgOralApotex Corporation2012-01-25Not applicableCanada
Auro-losartanTablet50.0 mgOralAuro Pharma Inc2013-03-26Not applicableCanada
Auro-losartanTablet100.0 mgOralAuro Pharma Inc2013-03-26Not applicableCanada
Auro-losartanTablet25.0 mgOralAuro Pharma Inc2013-03-26Not applicableCanada
Bio-losartanTablet25 mgOralBiomed Pharma2016-05-09Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Act Losartan/hctLosartan Potassium (100 mg) + Hydrochlorothiazide (12.5 mg)TabletOralActavis Pharma Company2012-07-03Not applicableCanada
Act Losartan/hctLosartan Potassium (50 mg) + Hydrochlorothiazide (12.5 mg)TabletOralActavis Pharma Company2012-07-03Not applicableCanada
Act Losartan/hctLosartan Potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralActavis Pharma Company2012-07-03Not applicableCanada
Ag-losartan HctzLosartan Potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-losartan HctzLosartan Potassium (50 mg) + Hydrochlorothiazide (12.5 mg)TabletOralAngita Pharma Inc.Not applicableNot applicableCanada
Apo-losartan/hctzLosartan Potassium (100 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex Corporation2012-01-25Not applicableCanada
Apo-losartan/hctzLosartan Potassium (50 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex Corporation2012-01-25Not applicableCanada
Apo-losartan/hctzLosartan Potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralApotex Corporation2012-01-25Not applicableCanada
Auro-losartan HctLosartan Potassium (100 mg) + Hydrochlorothiazide (25 mg)TabletOralAuro Pharma Inc2014-04-29Not applicableCanada
Auro-losartan HctLosartan Potassium (100 mg) + Hydrochlorothiazide (12.5 mg)TabletOralAuro Pharma Inc2014-04-29Not applicableCanada
International/Other Brands
Lortaan
Categories
UNII
JMS50MPO89
CAS number
114798-26-4
Weight
Average: 422.911
Monoisotopic: 422.162187095
Chemical Formula
C22H23ClN6O
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

Pharmacology

Indication

May be used as a first line agent to treat uncomplicated hypertension, isolated systolic hypertension and left ventricular hypertrophy. May be used as a first line agent to delay progression of diabetic nephropathy. Losartan may be also used as a second line agent in the treatment of congestive heart failure, systolic dysfunction, myocardial infarction and coronary artery disease in those intolerant of ACE inhibitors.

Associated Conditions
Pharmacodynamics

Losartan is the first of a class of antihypertensive agents called angiotensin II receptor blockers (ARBs). Losartan and its longer acting active metabolite, E-3174, are specific and selective type-1 angiotensin II receptor (AT1) antagonists which block the blood pressure increasing effects angiotensin II via the renin-angiotensin-aldosterone system (RAAS). RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: AT1 and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure.

Mechanism of action

Losartan competitively inhibits the binding of angiotensin II to AT1 in many tissues including vascular smooth muscle and the adrenal glands. Losartan is metabolized to its active metabolite, E-3174, which is 10 to 40 times more potent than losartan and acts as a non-competitive AT1 antagonist. Inhibition of angiotensin II binding to AT1 inhibits its AT1-mediated vasoconstrictive and aldosterone-secreting effects and results in decreased vascular resistance and blood pressure. Losartan is 1,000 times more selective for AT1 than AT2. Inhibition of aldosterone secretion may increase sodium and water excretion while decreasing potassium excretion. Losartan is effective for reducing blood pressure and may be used to treat essential hypertension, left ventricular hypertrophy and diabetic nephropathy.

TargetActionsOrganism
AType-1 angiotensin II receptor
antagonist
Human
Absorption

Losartan is well absorbed and undergoes substantial first-pass metabolism; the systemic bioavailability of losartan is approximately 33%. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 3-4 hours, respectively. While maximum plasma concentrations of losartan and its active metabolite are approximately equal, the AUC of the metabolite is about 4 times as great as that of losartan. When given with a meal, absorption is slows down and Cmax decreases.

Volume of distribution
  • 34 L [losartan, healthy subjects]
  • 12 L [active metabolite, healthy subjects]
Protein binding

99.7% protein bound, primarily to albumin

Metabolism

Hepatic. Losartan is metabolized to a 5-carboxylic acid derivative (E-3174) via an aldehyde intermediate (E-3179) primarily by cytochrome P450 (CYP) 2C9 and CYP3A4. E-3174 is an active metabolite with 10- to 40-fold higher potency than its parent compound, losartan. Approxiamtely 14% of losartan is converted to E-3174; however, the AUC of E-3174 was found to be 4- to 8-fold higher than losartan and E-3174 is considered the main contributor to the pharmacologic effects of this medication.

Route of elimination

Following oral administration of losartan, 35% of the dose is recovered in the urine and about 60% in the feces. Following an intravenous dose, 45% is recovered in the urine and 50% in the feces.

Half life

The terminal t1/2 of losartan is 2 hours. The active metabolite has a half-life of 6-9 hours.

Clearance
  • Total plasma clearance = 600 mL/min Losartan
  • Total plasma clearance = 50 mL/min [active metabolite]
  • Renal clearance = 75 mL/min Losartan
  • Renal clearance = 25 mL/min [active metabolite]
Toxicity

Hypotension and tachycardia; Bradycardia could occur from parasympathetic (vagal) stimulation, LD50= 1000 mg/kg (orally in rat)

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Losartan.
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Losartan.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Losartan.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Losartan.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Losartan.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Losartan.
6-Deoxyerythronolide BThe metabolism of Losartan can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Losartan.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Losartan.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Losartan.
Food Interactions
  • Take without regard to meals. Take at same time each day. Food delays absorption, but does not affect the extent of absorption.

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. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H: Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002 Mar 23;359(9311):995-1003. [PubMed:11937178]
  2. Guo ZX, Qiu MC: [Losartan downregulates the expression of transforming growth factor beta type I and type II receptors in kidney of diabetic rat]. Zhonghua Nei Ke Za Zhi. 2003 Jun;42(6):403-8. [PubMed:12895325]
  3. Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC: Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006 Apr 7;312(5770):117-21. [PubMed:16601194]
  4. Sica DA, Gehr TW, Ghosh S: Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814. [PubMed:16029066]
  5. Stanfield, Cindy L.;Germann, William J. (2009). Principles of Human Physiology (3rd ed.). Benjamin-Cummings Publishing Company. [ISBN:978-0321556660]
  6. Bader, M. (2004). Renin-angiotensin-aldosterone system. In Encyclopedic reference of molecular pharmacology (pp. 810-814). Berlin: Springer. [ISBN:9783540298328]
External Links
Human Metabolome Database
HMDB0014816
KEGG Drug
D08146
KEGG Compound
C07072
PubChem Compound
3961
PubChem Substance
46506538
ChemSpider
3824
BindingDB
82258
ChEBI
6541
ChEMBL
CHEMBL191
Therapeutic Targets Database
DAP000523
PharmGKB
PA450268
IUPHAR
590
Guide to Pharmacology
GtP Drug Page
HET
LSN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Losartan
ATC Codes
C09DA01 — Losartan and diureticsC09DB06 — Losartan and amlodipineC09CA01 — Losartan
AHFS Codes
  • 24:32.08 — Angiotensin Ii Receptor Antagonists
PDB Entries
5x23 / 5x24 / 5xxi
FDA label
Download (212 KB)
MSDS
Download (19 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingTreatmentMalignant Neoplasm of Pancreas1
0CompletedBasic SciencePeripheral Arterial Disease (PAD)1
0CompletedDiagnosticPostural Tachycardia Syndrome1
0CompletedTreatmentDiabetic Nephropathies1
0CompletedTreatmentSickle Cell Disorders1
0Not Yet RecruitingOtherCystic Fibrosis (CF)1
0Not Yet RecruitingTreatmentBlood Pressures / High Blood Pressure (Hypertension)1
1CompletedNot AvailableHealthy Volunteers11
1CompletedNot AvailableKidney Diseases1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHypertension(HTN)1
1CompletedDiagnosticCytochrome / Pharmacokinetics1
1CompletedDiagnosticHigh Blood Pressure (Hypertension)1
1CompletedHealth Services ResearchHealthy Volunteers2
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentCardiovascular Disease (CVD)1
1CompletedTreatmentFasting1
1CompletedTreatmentHigh Blood Pressure (Hypertension)4
1CompletedTreatmentHigh Blood Pressure (Hypertension) / Hyperlipidemias1
1TerminatedBasic ScienceHigh Blood Pressure (Hypertension) / Multiple System Atrophy (MSA) / Progressive autonomic failure1
1Unknown StatusTreatmentHealthy Volunteers1
1, 2CompletedTreatmentAging1
1, 2RecruitingTreatmentChildren / Pulmonary vein stenosis1
1, 2RecruitingTreatmentDisseminated Sclerosis1
1, 2RecruitingTreatmentHamstring Injury1
1, 2TerminatedTreatmentAlbinism, Oculocutaneous / Hermansky-Pudlak Syndrome (HPS) / Metabolic Diseases / Platelet Storage Pool Deficiency / Pulmonary Fibrosis1
2Active Not RecruitingTreatmentConnective Tissue Disorders / Oesophagitis, Eosinophilic1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentMalignant Neoplasm of Pancreas1
2CompletedNot AvailableDiabetes, Diabetes Mellitus Type 11
2CompletedPreventionHigh Blood Pressure (Hypertension) / Hyperlipidemias1
2CompletedPreventionInflammatory Reaction1
2CompletedPreventionSarcopenia1
2CompletedTreatmentChronic Kidney Disease (CKD) / High Blood Pressure (Hypertension) / Hyperkalemia1
2CompletedTreatmentDiabetic Macular Edema (DME)1
2CompletedTreatmentGlomerulosclerosis, Focal Segmental1
2CompletedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedTreatmentHigh Blood Pressure (Hypertension) / Severe Obstructive Sleep Apnea (Apnea Hypopnea Index > 30 Events/Hour)1
2CompletedTreatmentHypertrophic Cardiomyopathy2
2CompletedTreatmentMarfan Syndrome1
2CompletedTreatmentNAFLD1
2CompletedTreatmentRenal Dysfunction / Sickle Cell Disorders1
2CompletedTreatmentTransplant, Kidney1
2Not Yet RecruitingTreatmentMorquio A Syndrome / Morquio Syndrome / Morquio Syndrome A / MPS - Mucopolysaccharidosis / MPS IV A / MPS VI / Mucopolysaccharidoses / Mucopolysaccharidosis IV A / Mucopolysaccharidosis VI1
2RecruitingPreventionAging / High Blood Pressure (Hypertension) / Sedentary Lifestyle1
2RecruitingPreventionStress Disorders, Post-Traumatic1
2RecruitingTreatmentCystic Fibrosis (CF)1
2RecruitingTreatmentHeart Defects,Congenital / Tetralogy Of Fallot / Ventricular Dysfunction, Right1
2RecruitingTreatmentHigh Blood Pressure (Hypertension)2
2RecruitingTreatmentHigh Blood Pressure (Hypertension) / Kidney Diseases / Proteinuria / Sickle Cell Disorders1
2RecruitingTreatmentMalignant Neoplasm of Pancreas1
2RecruitingTreatmentNAFLD - Nonalcoholic Fatty Liver Disease1
2RecruitingTreatmentOesophagitis, Eosinophilic1
2TerminatedTreatmentHigh Blood Pressure (Hypertension)1
2TerminatedTreatmentHigh Blood Pressure (Hypertension) / Unspecified Adult Solid Tumor, Protocol Specific1
2TerminatedTreatmentPre-Diabetic / Pre-Hypertension1
2Unknown StatusPreventionMarfan Syndrome1
2Unknown StatusTreatmentHypertension,Essential1
2Unknown StatusTreatmentNonalcoholic Fatty Liver Disease / Nonalcoholic Steatohepatitis1
2, 3CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF) / Pulmonary Fibrosis1
2, 3RecruitingPreventionCognitively Normal Older Adults / Family History of Alzheimer's Disease / High Blood Pressure (Hypertension) / Subjective Cognitive Decline1
2, 3TerminatedTreatmentDiabetic Nephropathies1
2, 3WithdrawnTreatmentHigh Blood Pressure (Hypertension)1
3Active Not RecruitingTreatmentNewly-diagnosed Glioblastoma1
3CompletedPreventionLung Cancers / Nonvalvular Atrial Fibrillation1
3CompletedTreatmentArterial Hypertension1
3CompletedTreatmentBMI >27 kg/m2 / High Blood Pressure (Hypertension) / Left Ventricular Hypertrophy1
3CompletedTreatmentCardiovascular Disease (CVD) / High Blood Pressure (Hypertension)1
3CompletedTreatmentDiabetic Nephropathies1
3CompletedTreatmentDiabetic Nephropathies / Kidney Diseases / Proteinuria / Type 2 Diabetes Mellitus1
3CompletedTreatmentHeart Failure, Unspecified1
3CompletedTreatmentHigh Blood Pressure (Hypertension)16
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Metabolic Disorders1
3CompletedTreatmentHyperlipidemias / Hypertension,Essential1
3CompletedTreatmentHypertension,Essential2
3CompletedTreatmentHypertension,Essential / Impaired Renal Function1
3CompletedTreatmentHypertension; Hypertrophy, Left Ventricular1
3CompletedTreatmentIgA Glomerulonephritis1
3CompletedTreatmentMarfan Syndrome2
3CompletedTreatmentNonalcoholic Steatohepatitis1
3CompletedTreatmentProteinuria2
3CompletedTreatmentPulmonary Hypertension (PH)1
3Not Yet RecruitingTreatmentGlomerulonephritis, Immunoglobulin A (IgA)1
3Not Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
3RecruitingTreatmentCerebral Small Vessels Disease1
3RecruitingTreatmentChronic Kidney Disease (CKD)1
3RecruitingTreatmentHigh Blood Pressure (Hypertension)1
3RecruitingTreatmentMarfan Syndrome1
3TerminatedTreatmentHigh Blood Pressure (Hypertension)1
3TerminatedTreatmentKidney Diseases / Renal Dysfunction / Type 2 Diabetes Mellitus1
3TerminatedTreatmentMarfan Syndrome1
3Unknown StatusPreventionMarfan Syndrome1
3Unknown StatusTreatmentDiabetes Mellitus (DM) / Hypertension,Essential1
3Unknown StatusTreatmentMarfan Syndrome1
3Unknown StatusTreatmentSevere Sepsis1
3WithdrawnPreventionHyperoxaluria1
3WithdrawnTreatmentEssential Arterial Hypertension2
4Active Not RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4CompletedBasic ScienceRejection, Transplant1
4CompletedDiagnosticHyperaldosteronism1
4CompletedOtherBMI >30 kg/m2 / High Blood Pressure (Hypertension) / Hyperglycemias1
4CompletedPreventionDiabetic Nephropathies1
4CompletedPreventionKidney Diseases / Proteinuria1
4CompletedPreventionRenal Stones1
4CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Fibrosis, Liver1
4CompletedTreatmentCongestive Heart Failure (CHF) / Low Cardiac Output1
4CompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4CompletedTreatmentDiabetic Nephropathies / High Blood Pressure (Hypertension)1
4CompletedTreatmentHeart Failure, Unspecified1
4CompletedTreatmentHigh Blood Pressure (Hypertension)8
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Hypertension,Essential1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Impaired Glucose Tolerance (IGT)1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Insulin Resistance / Metabolic Syndromes1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Left Ventricle Hypertrophy1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Pharmacogenetics1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Sleep Apnea Syndrome1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Strokes1
4CompletedTreatmentInfection, Human Immunodeficiency Virus I1
4CompletedTreatmentKidney Diseases1
4CompletedTreatmentLiver Transplant Recipients1
4CompletedTreatmentMacroalbuminuric Diabetic Nephropathy1
4CompletedTreatmentStage 2 Systolic Hypertension1
4CompletedTreatmentStroke, Ischemic1
4Enrolling by InvitationSupportive CareColectomy / Opioids Use / Postoperative pain / Surgery, Colorectal1
4Not Yet RecruitingTreatmentHypertension;Nephropathy1
4RecruitingBasic ScienceArterial hypoxia / Chemoreceptor Apnea / Respiration; Sleep Disorder / Sleep Disordered Breathing (SDB)1
4RecruitingPreventionBlood Pressures / High Blood Pressure (Hypertension) / Strokes1
4RecruitingTreatmentAortic Valve Insufficiency / Aortic Valve Stenosis / High Blood Pressure (Hypertension) / Left Ventricular Hypertrophy / LVM1
4RecruitingTreatmentArterial Hypertension / High Blood Pressure (Hypertension)1
4RecruitingTreatmentBipolar Disorder (BD) / Cardiovascular Disease (CVD) / Major Depressive Disorder (MDD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Serious Mental Illness1
4RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
4RecruitingTreatmentEmphysema1
4RecruitingTreatmentGlomerulonephritis / Proteinuria1
4RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4RecruitingTreatmentIgA Nephropathy1
4RecruitingTreatmentPediatric Hypertension1
4SuspendedTreatmentEnd Stage Renal Disease (ESRD) / High Blood Pressure (Hypertension) / Proteinuria1
4TerminatedPreventionAtherosclerosis / Carotid Artery Stenosis / Strokes1
4TerminatedPreventionDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4TerminatedTreatmentAnalgesia / Aspiration / Pain NOS / Tibial Fractures1
4Unknown StatusPreventionAlcoholic Liver Cirrhosis / Ascites1
4Unknown StatusTreatmentBlood Pressures1
4Unknown StatusTreatmentChronic Bronchitis / Chronic Obstructive Pulmonary Disease (COPD) / Emphysema / Smoking1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension)3
4Unknown StatusTreatmentHypertension, Resistant to Conventional Therapy / Hypertension,Essential1
4Unknown StatusTreatmentHypertension,Essential1
4WithdrawnTreatmentHeart Failure, Unspecified1
Not AvailableCompletedNot AvailableAging / High Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableHealthy Normotensive Participants1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)2
Not AvailableCompletedNot AvailableHypertrophic Cardiomyopathy / Left Ventricular Hypertrophy / Myocardial Ischemia1
Not AvailableCompletedBasic ScienceHealthy Volunteers1
Not AvailableCompletedBasic ScienceInsulin Resistance / Type 2 Diabetes Mellitus1
Not AvailableCompletedBasic ScienceMemory, Long-Term / Memory, Short-Term1
Not AvailableCompletedDiagnosticHigh Blood Pressure (Hypertension)1
Not AvailableCompletedPreventionLeft Ventricular Hypertrophy / Renal Failure1
Not AvailableCompletedTreatmentAlbuminuria1
Not AvailableCompletedTreatmentAngiotensin II Type 1 Receptor Blockers / Diabetic Nephropathies / Glucose Metabolism / Obese / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / Impaired Glucose Tolerance (IGT) / Insulin Resistance / Pre-Diabetic1
Not AvailableCompletedTreatmentDiabetic Nephropathies1
Not AvailableCompletedTreatmentDiabetic Nephropathies / Proteinuria1
Not AvailableCompletedTreatmentDiabetic Nephropathies / Type 2 Diabetes Mellitus2
Not AvailableCompletedTreatmentDuchenne's Muscular Dystrophy (DMD) / Prophylaxis of cardiomyopathy1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)6
Not AvailableCompletedTreatmentMicroalbuminuria1
Not AvailableCompletedTreatmentPrecancerous Conditions1
Not AvailableRecruitingNot AvailableObesity, Morbid1
Not AvailableRecruitingBasic ScienceChronic Bronchitis / Chronic Obstructive Pulmonary Disease (COPD)1
Not AvailableRecruitingBasic ScienceHealthy Volunteers1
Not AvailableRecruitingPreventionAtherosclerosis / Nephritis, Lupus1
Not AvailableRecruitingTreatmentIgA Nephropathy1
Not AvailableRecruitingTreatmentPosttraumatic Stress Disorders1
Not AvailableTerminatedScreeningCytochrome P450 Phenotype and Genotype Metrics1
Not AvailableTerminatedTreatmentACE Inhibitor / Angiotensin II Type 1 Receptor Blockers / Dose-Response Relationship, Drug / Progression, Disease / Proteinuria / Renal Insufficiency,Chronic1
Not AvailableTerminatedTreatmentRenal Insufficiency,Chronic1
Not AvailableUnknown StatusNot AvailableAtherosclerosis / Diabetes Mellitus (DM)1
Not AvailableUnknown StatusNot AvailableHigh Blood Pressure (Hypertension)2
Not AvailableUnknown StatusTreatmentAngiotensin II Type 1 Receptor Blockers / Angiotensin-Converting Enzyme Inhibitors / Kidney Insufficiency, Chronic / Proteinuria1
Not AvailableUnknown StatusTreatmentBicuspid Aortic Valve (BAV) / Thoracic Aortic Aneurysm (TAA)1
Not AvailableUnknown StatusTreatmentChronic Renal Diseases1
Not AvailableUnknown StatusTreatmentIgA Glomerulonephritis1
Not AvailableUnknown StatusTreatmentNonvalvular Atrial Fibrillation1
Not AvailableWithdrawnSupportive CareDyspnea / Lung Cancers / Pulmonary Complications / Radiation Fibrosis1

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
TabletOral100.0 mg
TabletOral25.0 mg
TabletOral50.0 mg
TabletOral100 mg
TabletOral25 mg
TabletOral50 mg
TabletOral
TabletOral100 mg/1
TabletOral25 mg/1
TabletOral50 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral
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
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Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5210079No1993-11-112010-11-11Us
US5608075No1992-03-042009-03-04Us
CA2085584No2003-02-112011-06-07Canada
CA1334092No1995-01-242012-01-24Canada

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)184 °CPhysProp
water solubility0.82 mg/LNot Available
logP6.1Not Available
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

Taxonomy

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
Biphenyl / Phenyltetrazole / 1,2,4,5-tetrasubstituted imidazole / Aryl chloride / Aryl halide / N-substituted imidazole / Azole / Heteroaromatic compound / Imidazole / Tetrazole
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, biphenylyltetrazole (CHEBI:6541)

Targets

Kind
Protein
Organism
Human
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
Human
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  6. FDA label Losartan [File]
Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. 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
Human
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
Human
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
Human
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
Human
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
Human
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]

Carriers

Kind
Protein
Organism
Human
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

Transporters

Kind
Protein
Organism
Human
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
Human
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
Human
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
Human
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
Human
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, 2018 20:25