Identification

Name
Ezetimibe
Accession Number
DB00973
Description

Ezetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and phytosterol absorption. The discovery and research of this drug began in the early 1990s, after the intravenous administration of radiolabelled ezetimibe in rats revealed that it was being localized within enterocytes of the intestinal villi - this prompted studies investigating the effect of ezetimibe on intestinal cholesterol absorption.3 Ezetimibe is used as an adjunctive therapy to a healthy diet to lower cholesterol levels in primary hyperlipidemia, mixed hyperlipidemia, homozygous familial hypercholesterolemia (HoFH), and homozygous sitosterolemia (phytosterolemia).5

Unlike other classes of cholesterol-reducing compounds including statins and bile acid sequestrants, ezetimibe has a distinct mechanism of action involving the sterol transporter Niemann-Pick C1-Like 1 (NPC1L1), and is unique in that it does not affect the absorption of fat-soluble nutrients such as fat-soluble vitamins, triglycerides, or bile acids.4 In genetically NPC1L1-deficient mice, a 70% reduction in intestinal cholesterol absorption was seen, and these mice were insensitive to ezetimibe treatment - it was determined based on these findings that NPC1L1 plays an essential role in promoting intestinal cholesterol uptake via an ezetimibe-sensitive pathway.3 By interfering with the intestinal uptake of cholesterol and phytosterols, ezetimibe reduces the delivery of intestinal cholesterol to the liver.5

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 409.4252
Monoisotopic: 409.148949953
Chemical Formula
C24H21F2NO3
Synonyms
  • Ezetimiba
  • ézétimibe
  • Ezetimibe
  • Ezetimibum
External IDs
  • MK0653
  • SCH 58235
  • SCH-58235
  • SCH58235

Pharmacology

Indication

Ezetimibe is indicated to reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with primary hyperlipidemia, alone or in combination with an HMG-CoA reductase inhibitor (statin).5,6,7 It is also indicated to reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with mixed hyperlipidemia in combination with fenofibrate, and to reduce elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH), in combination with atorvastatin or simvastatin.5 Ezetimibe may also be used to reduce elevated sitosterol and campesterol in patients with homozygous sitosterolemia (phytosterolemia).5

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

Ezetimibe was shown to reduce the levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG), and increase high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia.5 This therapeutic effect was more profound when ezetimibe was co-administered with a statin or fenofibrate compared to either treatment alone.5 In clinical trials involving patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia, a recommended therapeutic dose of ezetimibe was effective in reducing the LDL levels by 15-20% while increasing HDL-C by 2.5-5%.4

The effects of increased exposure to ezetimibe secondary to moderate-severe hepatic impairment have not been assessed - patients meeting these criteria should avoid the use of ezetimibe.5 Post-marketing reports indicate the potential for myopathy and rhabdomyolysis in patients taking ezetimibe, and this risk appears to be exacerbated in patients concurrently receiving, or having recently received, statin therapy.5

Mechanism of action

Ezetimibe mediates its blood cholesterol-lowering effect via selectively inhibiting the absorption of cholesterol and phytosterol by the small intestine without altering the absorption of fat-soluble vitamins and nutrients.3 The primary target of ezetimibe is the cholesterol transport protein Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is expressed on enterocytes/gut lumen (apical) as well as the hepatobiliary (canalicular) interface and plays a role in facilitating internalization of free cholesterol into the enterocyte in conjunction with the adaptor protein 2 (AP2) complex and clathrin.2 Once cholesterol in the gut lumen or bile is incorporated into the cell membrane of enterocytes, it binds to the sterol-sensing domain of NPC1L1 and forms a NPC1L1/cholesterol complex. The complex is then internalized or endocytosed by joining to AP2 clathrin, forming a vesicle complex that is translocated for storage in the endocytic recycling compartment.2

Ezetimibe does not require exocrine pancreatic function for its pharmacological activity; rather, it localizes and appears to act at the brush border of the small intestine. Ezetimibe selectively blocks the NPC1L1 protein in the jejunal brush border, reducing the uptake of intestinal lumen micelles into the enterocyte.2 Overall, ezetimibe causes a decrease in the delivery of intestinal cholesterol to the liver and reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood. While the full mechanism of action of ezetimibe in reducing the entry of cholesterol into both enterocytes and hepatocytes is not fully understood, one study proposed that ezetimibe prevents the NPC1L1/sterol complex from interacting with AP2 in clathrin coated vesicles and induces a conformational change in NPC1L1, rendering it incapable of binding to sterols.2 Another study suggested that ezetimibe disrupts the function of other protein complexes involved in regulating cholesterol uptake, including the CAV1–annexin 2 heterocomplex.2

TargetActionsOrganism
ANiemann-Pick C1-like protein 1
inhibitor
Humans
ASterol O-acyltransferase 1
inhibitor
Humans
UAminopeptidase N
other
Humans
Absorption

Administration of a single 10-mg dose of ezetimibe in fasted adults resulted in peak plasma concentrations (Cmax) of 3.4-5.5 ng/mL within 4-12 hours (Tmax).5 The Cmax of the major pharmacologically-active metabolite, ezetimibe-glucuronide, was 45-71 ng/mL and its Tmax was 1-2 hours.5 Food consumption has minimal effect on ezetimibe absorption, but the Cmax is increased by 38% when administered alongside a high-fat meal.5 The true bioavailability of ezetimibe cannot be determined, as it is insoluble in aqueous media suitable for intravenous injection.5

Volume of distribution

The relative volume of distribution of ezetimibe is 107.5L.10

Protein binding

Ezetimibe and ezetimibe-glucuronide are >90% bound to human plasma proteins.5 The mean in vitro protein binding ranged from 99.5% to 99.8% for ezetimibe and 87.8% to 92.0% for ezetimibe-glucuronide.3

Metabolism

In humans, ezetimibe is rapidly and extensively metabolized via a phase II glucuronide conjugation reaction in the small intestine and liver to form its main phenolic metabolite, ezetimibe glucuronide. The main human liver and/or intestinal uridine 5′-diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes responsible for the glucuronidation of ezetimibe were shown to be UGT1A1, 1A3, and 2B15 in vitro.3 Minimal phase I reaction involving oxidation of ezetimibe also occurs to form SCH 57871, and human jejunum microsomes also produced trace levels of a benzylic glucuronide (SCH 488128).3 Ezetimibe glucuronide accounts for 80-90% of the total circulating compound in plasma, and retains some pharmacological activity in inhibiting intestinal cholesterol uptake.5 In humans, ezetimibe and ezetimibe-glucuronide constitutes approximately 93% of the total drug in plasma.5 Plasma concentration-time profiles exhibit multiple peaks, suggestive of enterohepatic recycling5, and about 20% of the drug distributed is reabsorbed due to enterohepatic recirculation.10

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Route of elimination

Approximately 78% and 11% of orally administered radiolabelled ezetimibe are recovered in the feces and urine, respectively.5 Unchanged parent drug is the major component in feces and accounts for approximately 69% of an administered dose, while ezetimibe-glucuronide is the major component in urine and accounts for approximately 9% of an administered dose.5 High recovery of unchanged parent drug in feces suggests low absorption and/or hydrolysis of ezetimibe-glucuronide secreted in the bile.3

Half-life

Both ezetimibe and ezetimibe-glucuronide display an approximate half-life of 22 hours.5

Clearance

There are no pharmacokinetic data available on the clearance of ezetimibe.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Oral LD50 and intraperitoneal LD50 in rat were >2000 mg/kg.9 Estimated oral LD50 values in mouse and dog are >5000 mg/kg and >3000 mg/kg, respectively.9 One case of accidental overdose occurred in clinical studies in one female patient with homozygous sitosterolemia receiving 120 mg/day for 28 days with no reported clinical or laboratory adverse events.5 In case of overdose, symptomatic treatment is recommended.5

Affected organisms
  • Humans and other mammals
Pathways
Not Available
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
AbemaciclibAbemaciclib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
AcetylcysteineThe excretion of Ezetimibe can be decreased when combined with Acetylcysteine.
AdenineThe metabolism of Ezetimibe can be decreased when combined with Adenine.
AfatinibAfatinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
AlectinibAlectinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Aminohippuric acidThe excretion of Ezetimibe can be decreased when combined with Aminohippuric acid.
AmitriptylineThe metabolism of Ezetimibe can be decreased when combined with Amitriptyline.
AmprenavirThe excretion of Ezetimibe can be decreased when combined with Amprenavir.
ApalutamideApalutamide may increase the excretion rate of Ezetimibe which could result in a lower serum level and potentially a reduction in efficacy.
AstemizoleAstemizole may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
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

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Food Interactions
  • Take with or without food. Co-administration with food does not affect absorption.

Products

Product Images
International/Other Brands
Ezedoc / Ezetib / Zient
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act EzetimibeTabletOralActavis Pharma Company2014-09-152018-06-12Canada flag
EzetimibeTablet10 mgOralLaboratoire Riva Inc2018-08-14Not applicableCanada flag
EzetimibeTablet10 mgOralSivem Pharmaceuticals Ulc2014-09-16Not applicableCanada flag
EzetimibeTablet10 mgOralPro Doc Limitee2014-09-17Not applicableCanada flag
EzetimibeTablet10 mgOralSanis Health Inc2014-10-08Not applicableCanada flag
EzetrolTabletOralMerck Ltd.2003-06-15Not applicableCanada flag
Gln-ezetimibeTabletOralGlenmark Pharmaceuticals, Inc2019-07-23Not applicableCanada flag
M-ezetimibeTabletOralMantra Pharma Inc2017-12-142020-04-06Canada flag
Nra-ezetimibeTabletOralNora Pharma Inc2018-12-10Not applicableCanada flag
ZetiaTablet10 mg/1OralMed Pharma Co., Ltd.2011-04-102012-04-30US 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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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-ezetimibeTabletOralAccord Healthcare Inc2014-09-17Not applicableCanada flag
Ag-ezetimibeTabletOralAngita Pharma Inc.2018-07-20Not applicableCanada flag
Apo-ezetimibeTabletOralApotex Corporation2014-09-23Not applicableCanada flag
Auro-ezetimibeTabletOralAuro Pharma Inc2018-04-25Not applicableCanada flag
Bio-ezetimibeTabletOralBiomed Pharma2014-10-08Not applicableCanada flag
EzetimibeTablet10 mg/1Oralbryant ranch prepack2017-06-122017-12-31US flag
EzetimibeTablet10 mg/1OralAmerican Health Packaging2017-01-262019-09-30US flag
EzetimibeTablet10 mg/1Oralbryant ranch prepack2017-06-12Not applicableUS flag
EzetimibeTablet10 mg/1OralREMEDYREPACK INC.2019-01-092020-06-01US flag
EzetimibeTablet10 mg/1Oralbryant ranch prepack2017-06-12Not applicableUS 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
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (10 mg/1)TabletOralAmneal Pharmaceuticals NY LLC2017-11-21Not applicableUS flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 mg/1)TabletOralDr.Reddys Laboratories Inc2017-04-26Not applicableUS flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (10 mg/1)TabletOralGolden State Medical Supply2017-04-26Not applicableUS flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (20 mg/1)TabletOralNorthStar Rx LLC2019-08-19Not applicableUS flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (80 mg/1)TabletOralAscend Laboratories, LLC2017-12-24Not applicableUS flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 mg/1)TabletOralREMEDYREPACK INC.2019-03-13Not applicableUS flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 mg/1)Tablet, film coatedOralImpax Generics2017-04-262020-03-31US flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 mg/1)TabletOralREMEDYREPACK INC.2019-02-052020-06-01US flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (10 mg/1)TabletOralAscend Laboratories, LLC2017-12-24Not applicableUS flag
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (20 mg/1)TabletOralActavis Pharma, Inc.2017-04-26Not applicableUS flag

Categories

ATC Codes
C10BA02 — Simvastatin and ezetimibeC10BA05 — Atorvastatin and ezetimibeC10AX09 — EzetimibeC10BA06 — Rosuvastatin and ezetimibe
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as monobactams. These are compounds comprising beta-lactam ring is alone and not fused to another ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Monobactams
Alternative Parents
Phenylazetidines / Fluorobenzenes / 1-hydroxy-2-unsubstituted benzenoids / Aryl fluorides / Tertiary carboxylic acid amides / Secondary alcohols / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organofluorides
show 4 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / 1-phenylazetidine / 2-phenylazetidine / Alcohol / Aromatic alcohol / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azetidine
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, azetidines, beta-lactam (CHEBI:49040)

Chemical Identifiers

UNII
EOR26LQQ24
CAS number
163222-33-1
InChI Key
OLNTVTPDXPETLC-XPWALMASSA-N
InChI
InChI=1S/C24H21F2NO3/c25-17-5-1-15(2-6-17)22(29)14-13-21-23(16-3-11-20(28)12-4-16)27(24(21)30)19-9-7-18(26)8-10-19/h1-12,21-23,28-29H,13-14H2/t21-,22+,23-/m1/s1
IUPAC Name
(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one
SMILES
[H][[email protected]]1(CC[[email protected]](O)C2=CC=C(F)C=C2)C(=O)N(C2=CC=C(F)C=C2)[[email protected]]1([H])C1=CC=C(O)C=C1

References

Synthesis Reference

Venkataraman Sundaram, Srinivasam Rajan, Vaddadi Ramayya, Sunkara Vardhan, Bulusu Subrahmanyam, Cheemalapati Sasikala, "Polymorphs of ezetimibe and process for preparation thereof." U.S. Patent US20050171080, issued August 04, 2005.

US20050171080
General References
  1. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. [PubMed:15928087]
  2. Phan BA, Dayspring TD, Toth PP: Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415-27. doi: 10.2147/VHRM.S33664. Epub 2012 Jul 3. [PubMed:22910633]
  3. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634]
  4. Nutescu EA, Shapiro NL: Ezetimibe: a selective cholesterol absorption inhibitor. Pharmacotherapy. 2003 Nov;23(11):1463-74. [PubMed:14620392]
  5. FDA Approved Drug Products: Zetia (ezetimibe) oral tablets [Link]
  6. FDA Approved Drug Products: Liptruzet (ezetimibe/atorvastatin) oral tablets [Link]
  7. FDA Approved Drug Products: Vytorin (ezetimibe/simvastatin) oral tablets [Link]
  8. CaymanChem: Ezetimibe MSDS [Link]
  9. Health Canada Product Monograph: Ezetimibe oral tablets [Link]
  10. Getz Pharma: Ezita (Ezetimibe 10mg tablets) Product Label [File]
Human Metabolome Database
HMDB0015108
KEGG Drug
D01966
PubChem Compound
150311
PubChem Substance
46507625
ChemSpider
132493
BindingDB
50371521
RxNav
341248
ChEBI
49040
ChEMBL
CHEMBL1138
ZINC
ZINC000003810860
Therapeutic Targets Database
DAP000717
PharmGKB
PA10816
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ezetimibe
AHFS Codes
  • 24:06.05 — Cholesterol Absorption Inhibitors
FDA label
Download (350 KB)
MSDS
Download (281 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableDyslipidemia / Vascular Diseases1
4CompletedBasic ScienceAtherosclerosis1
4CompletedBasic ScienceDeficiency, Vitamin D1
4CompletedBasic ScienceHigh Cholesterol1
4CompletedDiagnosticHealthy Men1
4CompletedDiagnosticST Segment Elevation Myocardial Infarction (STEMI)1
4CompletedHealth Services ResearchPeripheral Arterial Disease (PAD)1
4CompletedPreventionAtrial Fibrillation (AF) / Hemostasis / Inflammatory Reaction / Magnetic Resonance Imaging (MRI) / Neuropsychology1
4CompletedPreventionCardiovascular Heart Disease2
4CompletedPreventionChronic Kidney Disease (CKD)1

Pharmacoeconomics

Manufacturers
  • Msp singapore co llc
Packagers
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Cardinal Health
  • Diversified Healthcare Services Inc.
  • Lake Erie Medical and Surgical Supply
  • Merck & Co.
  • MSP Distribution Services LLC
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Quality Care
  • Resource Optimization and Innovation LLC
  • Schering-Plough Inc.
  • Vangard Labs Inc.
Dosage Forms
FormRouteStrength
Tablet, coatedOral5 mg
Tablet10 MG
Capsule, liquid filledOral10 mg
Tablet, coatedOral10 mg
Tablet, film coatedOral10 mg
Tablet, coatedOral20 mg
Tablet, film coatedOral
TabletOral
Tablet, film coated10 mg
Tablet, coatedOral40 mg
TabletOral10 mg
TabletOral
Tablet
TabletOral10 mg/1
Prices
Unit descriptionCostUnit
Zetia 10 mg tablet5.15USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5846966No1998-12-082013-09-21US flag
US5969156Yes1999-10-192017-01-08US flag
USRE37721Yes2002-05-282017-04-25US flag
USRE42461Yes2011-06-142017-04-25US flag
US7612058Yes2009-11-032026-04-30US flag
US7030106Yes2006-04-182022-07-25US flag
US7335799No2008-02-262025-12-03US flag
US9624152No2017-04-182023-12-23US flag
US8497301No2013-07-302023-12-23US flag
US9000041No2015-04-072023-12-23US flag
US10118881No2018-11-062023-12-23US flag
Additional Data Available
  • Filed On
    Filed On

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

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)163°C FDA label
water solubilityPractically insoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00846 mg/mLALOGPS
logP4.14ALOGPS
logP4.56ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)9.48ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area60.77 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity108.86 m3·mol-1ChemAxon
Polarizability41.65 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9899
Blood Brain Barrier+0.9074
Caco-2 permeable-0.5225
P-glycoprotein substrateNon-substrate0.6918
P-glycoprotein inhibitor INon-inhibitor0.6026
P-glycoprotein inhibitor IIInhibitor0.5306
Renal organic cation transporterNon-inhibitor0.8659
CYP450 2C9 substrateNon-substrate0.8244
CYP450 2D6 substrateNon-substrate0.7505
CYP450 3A4 substrateSubstrate0.5341
CYP450 1A2 substrateNon-inhibitor0.7013
CYP450 2C9 inhibitorNon-inhibitor0.6125
CYP450 2D6 inhibitorNon-inhibitor0.8442
CYP450 2C19 inhibitorNon-inhibitor0.5807
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5289
Ames testNon AMES toxic0.7476
CarcinogenicityNon-carcinogens0.8328
BiodegradationNot ready biodegradable0.9853
Rat acute toxicity2.4979 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9767
hERG inhibition (predictor II)Inhibitor0.5455
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-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-1910000000-5b24d4adc8cd3de959fc

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rab gtpase binding
Specific Function
Plays a major role in cholesterol homeostasis. Is critical for the uptake of cholesterol across the plasma membrane of the intestinal enterocyte. Is the direct molecular target of ezetimibe, a drug...
Gene Name
NPC1L1
Uniprot ID
Q9UHC9
Uniprot Name
Niemann-Pick C1-like protein 1
Molecular Weight
148726.52 Da
References
  1. Altmann SW, Davis HR Jr, Zhu LJ, Yao X, Hoos LM, Tetzloff G, Iyer SP, Maguire M, Golovko A, Zeng M, Wang L, Murgolo N, Graziano MP: Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004 Feb 20;303(5661):1201-4. [PubMed:14976318]
  2. Wang J, Williams CM, Hegele RA: Compound heterozygosity for two non-synonymous polymorphisms in NPC1L1 in a non-responder to ezetimibe. Clin Genet. 2005 Feb;67(2):175-7. [PubMed:15679830]
  3. Sudhop T, Lutjohann D, von Bergmann K: Sterol transporters: targets of natural sterols and new lipid lowering drugs. Pharmacol Ther. 2005 Mar;105(3):333-41. Epub 2004 Dec 9. [PubMed:15737409]
  4. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, Crona JH, Davis HR Jr, Dean DC, Detmers PA, Graziano MP, Hughes M, Macintyre DE, Ogawa A, O'neill KA, Iyer SP, Shevell DE, Smith MM, Tang YS, Makarewicz AM, Ujjainwalla F, Altmann SW, Chapman KT, Thornberry NA: The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8132-7. Epub 2005 May 31. [PubMed:15928087]
  5. von Bergmann K, Sudhop T, Lutjohann D: Cholesterol and plant sterol absorption: recent insights. Am J Cardiol. 2005 Jul 4;96(1A):10D-14D. [PubMed:15992510]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sterol o-acyltransferase activity
Specific Function
Catalyzes the formation of fatty acid-cholesterol esters, which are less soluble in membranes than cholesterol. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition ...
Gene Name
SOAT1
Uniprot ID
P35610
Uniprot Name
Sterol O-acyltransferase 1
Molecular Weight
64733.975 Da
References
  1. Singh A, Basit A, Banerjee UC: Burkholderia cenocepacia: a new biocatalyst for efficient bioreduction of ezetimibe intermediate. J Ind Microbiol Biotechnol. 2009 Nov;36(11):1369-74. doi: 10.1007/s10295-009-0622-z. Epub 2009 Aug 8. [PubMed:19669185]
  2. Costet P: Molecular pathways and agents for lowering LDL-cholesterol in addition to statins. Pharmacol Ther. 2010 Jun;126(3):263-78. doi: 10.1016/j.pharmthera.2010.02.006. Epub 2010 Mar 19. [PubMed:20227438]
  3. Wang HH, Portincasa P, Mendez-Sanchez N, Uribe M, Wang DQ: Effect of ezetimibe on the prevention and dissolution of cholesterol gallstones. Gastroenterology. 2008 Jun;134(7):2101-10. doi: 10.1053/j.gastro.2008.03.011. Epub 2008 Mar 10. [PubMed:18442485]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Other
General Function
Zinc ion binding
Specific Function
Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogen...
Gene Name
ANPEP
Uniprot ID
P15144
Uniprot Name
Aminopeptidase N
Molecular Weight
109538.68 Da
References
  1. Kramer W, Girbig F, Corsiero D, Pfenninger A, Frick W, Jahne G, Rhein M, Wendler W, Lottspeich F, Hochleitner EO, Orso E, Schmitz G: Aminopeptidase N (CD13) is a molecular target of the cholesterol absorption inhibitor ezetimibe in the enterocyte brush border membrane. J Biol Chem. 2005 Jan 14;280(2):1306-20. Epub 2004 Oct 19. [PubMed:15494415]

Enzymes

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. Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [PubMed:21368751]
  2. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634]
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. Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [PubMed:21368751]
  2. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xeno...
Gene Name
UGT2B15
Uniprot ID
P54855
Uniprot Name
UDP-glucuronosyltransferase 2B15
Molecular Weight
61035.815 Da
References
  1. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S: Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004 Mar;32(3):314-20. [PubMed:14977865]
  2. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634]
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. Ghosal A, Hapangama N, Yuan Y, Achanfuo-Yeboah J, Iannucci R, Chowdhury S, Alton K, Patrick JE, Zbaida S: Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of ezetimibe (Zetia). Drug Metab Dispos. 2004 Mar;32(3):314-20. [PubMed:14977865]
  2. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
In vitro of human liver microsomes, the IC50 value was 7 μmol/L. In vivo follow-up studies suggest no clinically significant potential for interaction.
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. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
According to an in vitro assay, the IC50 value was 31 μmol/L in human liver microsomes. The FDA label indicates that this drug is unlikely to interact with CYP2C8 substrates.
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. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94. [PubMed:15871634]
  2. Ezetimibe FDA label [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [PubMed:21368751]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [PubMed:21368751]
  2. de Waart DR, Vlaming ML, Kunne C, Schinkel AH, Oude Elferink RP: Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702. doi: 10.1124/dmd.108.026146. Epub 2009 May 14. [PubMed:19443695]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. de Waart DR, Vlaming ML, Kunne C, Schinkel AH, Oude Elferink RP: Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702. doi: 10.1124/dmd.108.026146. Epub 2009 May 14. [PubMed:19443695]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Oswald S, Nassif A, Modess C, Keiser M, Ulrich A, Runge D, Hanke U, Lutjohann D, Engel A, Weitschies W, Siegmund W: Drug interactions between the immunosuppressant tacrolimus and the cholesterol absorption inhibitor ezetimibe in healthy volunteers. Clin Pharmacol Ther. 2011 Apr;89(4):524-8. doi: 10.1038/clpt.2011.4. Epub 2011 Mar 2. [PubMed:21368751]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. de Waart DR, Vlaming ML, Kunne C, Schinkel AH, Oude Elferink RP: Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009 Aug;37(8):1698-702. doi: 10.1124/dmd.108.026146. Epub 2009 May 14. [PubMed:19443695]
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 September 27, 2020 08:17

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