Identification
- Summary
Ezetimibe is a cholesterol absorption inhibitor used to lower total cholesterol, LDL-C, Apo-B, and non-HDL-C in primary hyperlipidemia and familial cholesterolemia.
- Brand Names
- Ezetrol, Lypqozet, Nexlizet, Roszet, Vytorin, Zetia
- Generic Name
- Ezetimibe
- DrugBank Accession Number
- DB00973
- Background
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
Structure for Ezetimibe (DB00973)
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used as adjunct in combination to manage Elevated blood lipids Regimen in combination with: Simvastatin (DB00641) •••••••••••• •••••• Used as adjunct in combination to manage Elevated blood lipids Regimen in combination with: Atorvastatin (DB01076) •••••••••••• •••••• Used as adjunct in combination to manage Elevated blood lipids Regimen in combination with: Fenofibrate (DB01039) •••••••••••• •••••• Used as adjunct in combination to manage Elevated blood lipids •••••••••••• •••••• Adjunct therapy in management of Elevated blood lipids •••••••••••• •••••• - Contraindications & Blackbox Warnings
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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
Target Actions Organism ANiemann-Pick C1-like protein 1 inhibitorHumans ASterol O-acyltransferase 1 inhibitorHumans UAminopeptidase N otherHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib Abemaciclib may decrease the excretion rate of Ezetimibe which could result in a higher serum level. Acetylcysteine The excretion of Ezetimibe can be decreased when combined with Acetylcysteine. Adenine The metabolism of Ezetimibe can be decreased when combined with Adenine. Afatinib Afatinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level. Alectinib Alectinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level. - Food Interactions
- Take with or without food. Co-administration with food does not affect absorption.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- International/Other Brands
- Ezedoc / Ezetib / Zient
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Ezetimibe Tablet 10 mg Oral Actavis Pharma Company 2014-09-15 2018-06-12 Canada 
Ezetimibe Tablet 10 mg Oral Sanis Health Inc 2014-10-08 Not applicable Canada Ezetimibe Tablet 10 mg Oral Laboratoire Riva Inc 2018-08-14 Not applicable Canada Ezetimibe Tablet 10 mg Oral Sivem Pharmaceuticals Ulc 2014-09-16 Not applicable Canada Ezetimibe Tablet 10 mg Oral Pro Doc Limitee 2014-09-17 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ach-ezetimibe Tablet 10 mg Oral Accord Healthcare Inc 2014-09-17 Not applicable Canada Ag-ezetimibe Tablet 10 mg Oral Angita Pharma Inc. 2018-07-20 Not applicable Canada Apo-ezetimibe Tablet 10 mg Oral Apotex Corporation 2014-09-23 Not applicable Canada Auro-ezetimibe Tablet 10 mg Oral Auro Pharma Inc 2018-04-25 Not applicable Canada Bio-ezetimibe Tablet 10 mg Oral Biomed Pharma 2014-10-08 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image AMISITELA Ezetimibe (10 MG) + Simvastatin (10 MG) Tablet Oral Pharmacare S.R.L. 2019-10-10 Not applicable Italy 
AMISITELA Ezetimibe (10 MG) + Simvastatin (20 MG) Tablet Oral Pharmacare S.R.L. 2019-10-10 Not applicable Italy AMISITELA Ezetimibe (10 MG) + Simvastatin (40 MG) Tablet Oral Pharmacare S.R.L. 2019-10-10 Not applicable Italy Arosuva plus Ezetimib 10 mg/10 mg Filmtabletten Ezetimibe (10 mg) + Rosuvastatin (10 mg) Tablet, film coated Oral Gebro Pharma Gmb H 2019-11-04 Not applicable Austria 
Arosuva plus Ezetimib 20 mg/10 mg Filmtabletten Ezetimibe (10 mg) + Rosuvastatin (20 mg) Tablet, film coated Oral Gebro Pharma Gmb H 2019-11-04 Not applicable Austria
Categories
- ATC Codes
- C10BA02 — Simvastatin and ezetimibe
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10BA — Combinations of various lipid modifying agents
- C10B — LIPID MODIFYING AGENTS, COMBINATIONS
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- C10AX — Other lipid modifying agents
- C10A — LIPID MODIFYING AGENTS, PLAIN
- C10 — LIPID MODIFYING AGENTS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- Anticholesteremic Agents
- Azetines
- BCRP/ABCG2 Substrates
- BSEP/ABCB11 Substrates
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Decreased Cholesterol Absorption
- Dietary Cholesterol Absorption Inhibitor
- Hypolipidemic Agents
- Hypolipidemic Agents Indicated for Hyperlipidemia
- Lipid Modifying Agents
- Lipid Modifying Agents, Plain
- Lipid Regulating Agents
- Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia
- OATP1B1/SLCO1B1 Substrates
- P-glycoprotein substrates
- UGT1A1 Substrates
- UGT1A3 substrates
- UGT2B7 substrates
- 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)
- Affected organisms
- Humans and other mammals
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][C@]1(CC[C@H](O)C2=CC=C(F)C=C2)C(=O)N(C2=CC=C(F)C=C2)[C@]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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Nutescu EA, Shapiro NL: Ezetimibe: a selective cholesterol absorption inhibitor. Pharmacotherapy. 2003 Nov;23(11):1463-74. [Article]
- FDA Approved Drug Products: Zetia (ezetimibe) oral tablets [Link]
- FDA Approved Drug Products: Liptruzet (ezetimibe/atorvastatin) oral tablets [Link]
- FDA Approved Drug Products: Vytorin (ezetimibe/simvastatin) oral tablets [Link]
- CaymanChem: Ezetimibe MSDS [Link]
- Health Canada Product Monograph: Ezetimibe oral tablets [Link]
- Getz Pharma: Ezita (Ezetimibe 10mg tablets) Product Label [File]
- External Links
- Human Metabolome Database
- HMDB0015108
- KEGG Drug
- D01966
- PubChem Compound
- 150311
- PubChem Substance
- 46507625
- ChemSpider
- 132493
- BindingDB
- 50371521
- 341248
- ChEBI
- 49040
- ChEMBL
- CHEMBL1138
- ZINC
- ZINC000003810860
- Therapeutic Targets Database
- DAP000717
- PharmGKB
- PA10816
- PDBe Ligand
- H56
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ezetimibe
- PDB Entries
- 7dfz / 8axw
- FDA label
- Download (350 KB)
- MSDS
- Download (281 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Heart Transplant Infection / Hepatitis C Virus (HCV) Infection / Transplanted Kidney Complication 1 4 Completed Basic Science Atherosclerosis 1 4 Completed Basic Science Deficiency, Vitamin D 1 4 Completed Basic Science High Cholesterol 1 4 Completed Diagnostic Healthy Men 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
Form Route Strength Tablet Oral 10.000 mg Tablet Oral 10.00 mg Tablet, coated Oral Tablet, film coated Oral 10 mg Tablet Oral Capsule, liquid filled Oral Capsule Oral Tablet, film coated Oral Tablet Oral 10.00 mg Tablet Oral 10.000 mg Tablet Oral 86.800 mg Tablet Oral Tablet Oral 10 mg/1 Tablet Oral 10 mg - Prices
Unit description Cost Unit Zetia 10 mg tablet 5.15USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5846966 No 1998-12-08 2013-09-21 US 
US5969156 Yes 1999-10-19 2017-01-08 US USRE37721 Yes 2002-05-28 2017-04-25 US USRE42461 Yes 2011-06-14 2017-04-25 US US7612058 Yes 2009-11-03 2026-04-30 US US7030106 Yes 2006-04-18 2022-07-25 US US7335799 No 2008-02-26 2025-12-03 US US9624152 No 2017-04-18 2023-12-23 US US8497301 No 2013-07-30 2023-12-23 US US9000041 No 2015-04-07 2023-12-23 US US10118881 No 2018-11-06 2023-12-23 US US10941095 No 2021-03-09 2023-12-23 US US10376470 No 2019-08-13 2033-05-01 US US9763885 No 2017-09-19 2033-05-01 US US10912751 No 2021-02-09 2036-03-14 US US11613511 No 2020-06-19 2040-06-19 US US11744816 No 2016-03-14 2036-03-14 US US11760714 No 2020-06-19 2040-06-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 163°C FDA label water solubility Practically insoluble FDA label - Predicted Properties
Property Value Source Water Solubility 0.00846 mg/mL ALOGPS logP 4.14 ALOGPS logP 4.56 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 9.48 Chemaxon pKa (Strongest Basic) -3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 60.77 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 108.86 m3·mol-1 Chemaxon Polarizability 41.65 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9899 Blood Brain Barrier + 0.9074 Caco-2 permeable - 0.5225 P-glycoprotein substrate Non-substrate 0.6918 P-glycoprotein inhibitor I Non-inhibitor 0.6026 P-glycoprotein inhibitor II Inhibitor 0.5306 Renal organic cation transporter Non-inhibitor 0.8659 CYP450 2C9 substrate Non-substrate 0.8244 CYP450 2D6 substrate Non-substrate 0.7505 CYP450 3A4 substrate Substrate 0.5341 CYP450 1A2 substrate Non-inhibitor 0.7013 CYP450 2C9 inhibitor Non-inhibitor 0.6125 CYP450 2D6 inhibitor Non-inhibitor 0.8442 CYP450 2C19 inhibitor Non-inhibitor 0.5807 CYP450 3A4 inhibitor Inhibitor 0.796 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5289 Ames test Non AMES toxic 0.7476 Carcinogenicity Non-carcinogens 0.8328 Biodegradation Not ready biodegradable 0.9853 Rat acute toxicity 2.4979 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9767 hERG inhibition (predictor II) Inhibitor 0.5455
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 216.5290497 predictedDarkChem Lite v0.1.0 [M-H]- 199.29549 predictedDeepCCS 1.0 (2019) [M+H]+ 217.2324497 predictedDarkChem Lite v0.1.0 [M+H]+ 201.69106 predictedDeepCCS 1.0 (2019) [M+Na]+ 216.1175497 predictedDarkChem Lite v0.1.0 [M+Na]+ 207.60358 predictedDeepCCS 1.0 (2019)
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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- von Bergmann K, Sudhop T, Lutjohann D: Cholesterol and plant sterol absorption: recent insights. Am J Cardiol. 2005 Jul 4;96(1A):10D-14D. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
Enzymes
- 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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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
- 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
- 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. [Article]
- 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. [Article]
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
- 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. [Article]
- 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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
- 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
- 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. [Article]
- 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
- 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. [Article]
- 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
- 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. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54