Identification

Name
Ezetimibe
Accession Number
DB00973  (APRD00619)
Type
Small Molecule
Groups
Approved
Description

Ezetimibe is an anti-hyperlipidemic medication which is used to lower cholesterol levels. Specifically, it appears to bind to a critical mediator of cholesterol absorption, the Niemann-Pick C1-Like 1 (NPC1L1) protein on the gastrointestinal tract epithelial cells as well as in hepatocytes.

Structure
Thumb
Synonyms
  • Ezedoc
  • Ezetimiba
  • Ezetimibum
  • Ezetrol
External IDs
MK0653 / SCH-58235 / SCH58235
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ach-ezetimibeTablet10 mgOralAccord Healthcare Limited2014-09-17Not applicableCanada
Act EzetimibeTablet10 mgOralActavis Pharma Company2014-09-15Not applicableCanada
Auro-ezetimibeTablet10 mgOralAuro Pharma IncNot applicableNot applicableCanada
Bio-ezetimibeTablet10 mgOralBiomed Pharma2014-10-08Not applicableCanada
EzetimibeTablet10 mg/1OralPrasco, Laboratories2017-05-22Not applicableUs
EzetimibeTablet10 mgOralSanis Health Inc2014-10-08Not applicableCanada
EzetimibeTablet10 mgOralPro Doc Limitee2014-09-17Not applicableCanada
EzetimibeTablet10 mgOralSivem Pharmaceuticals Ulc2014-09-16Not applicableCanada
EzetrolTablet10 mgOralMerck Ltd.2003-06-15Not applicableCanada
Gln-ezetimibeTablet10 mgOralGlenmark Pharmaceuticals, IncNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-ezetimibeTablet10 mgOralApotex Corporation2014-09-23Not applicableCanada
EzetimibeTablet10 mg/1OralActavis Pharma Company2017-06-12Not applicableUs
EzetimibeTablet10 mg/1OralPar Pharmaceutical2015-06-26Not applicableUs
EzetimibeTablet10 mg/1OralAv Kare, Inc.2017-06-15Not applicableUs
EzetimibeTablet10 mg/1OralAmerincan Health Packaging2017-02-01Not applicableUs
EzetimibeTablet10 mg/1OralAurobindo Pharma2017-08-25Not applicableUs
EzetimibeTablet10 mg/1OralApotex Corporation2017-06-12Not applicableUs
EzetimibeTablet10 mg/1OralZydus Pharmaceuticals Usa, Inc.2017-08-09Not applicableUs
EzetimibeTablet10 mg/1OralSandoz2017-06-12Not applicableUs
EzetimibeTablet10 mg/1OralA S Medication Solutions2016-12-122017-06-20Us
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EzetimibeTablet10 mg/1OralGolden State Medical Supply2017-11-06Not applicableUs
International/Other Brands
Ezedoc / Ezetib / Zetia / Zient
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (10 mg/1)TabletOralGolden State Medical Supply2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (10 mg/1)TabletOralDr. Reddy’s Laboratories Inc.2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (20 mg/1)Tablet, film coatedOralImpax Generics2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (80 mg/1)TabletOralGolden State Medical Supply2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (80 mg/1)TabletOralDr. Reddy’s Laboratories Inc.2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 mg/1)TabletOralActavis Pharma Company2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (20 mg/1)TabletOralGolden State Medical Supply2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (20 mg/1)TabletOralDr. Reddy’s Laboratories Inc.2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 mg/1)Tablet, film coatedOralImpax Generics2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (10 mg/1)TabletOralActavis Pharma Company2017-04-26Not applicableUs
Categories
UNII
EOR26LQQ24
CAS number
163222-33-1
Weight
Average: 409.4252
Monoisotopic: 409.148949953
Chemical Formula
C24H21F2NO3
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
O[[email protected]@H](CC[[email protected]@H]1[[email protected]](N(C1=O)C1=CC=C(F)C=C1)C1=CC=C(O)C=C1)C1=CC=C(F)C=C1

Pharmacology

Indication

For use as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia.

Structured Indications
Pharmacodynamics

Ezetimibe is in a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Ezetimibe, administered alone is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, and Apo B in patients with primary (heterozygous familial and non-familial) hypercholesterolemia. It is also used in combination therapy with HMG-CoA reductase inhibitors. Ezetimibe has a mechanism of action that differs from those of other classes of cholesterol-reducing compounds (HMG-CoA reductase inhibitors, bile acid sequestrants, fibric acid derivatives, and plant stanols). Ezetimibe does not inhibit cholesterol synthesis in the liver, or increase bile acid excretion but instead localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver. This causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood; this distinct mechanism is complementary to that of HMG-CoA reductase inhibitors.

Mechanism of action

Ezetimibe localizes and appears to act at the brush border of the small intestine and inhibits the absorption of cholesterol. This leads to a decrease in the delivery of intestinal cholesterol to the liver.

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

After oral administration, ezetimibe is absorbed and extensively conjugated to a pharmacologically active phenolic glucuronide (ezetimibe-glucuronide). When a single 10 mg dose of ezetimibe is given to a fasted, male, adult subject, the pharmacokinetic parameters are as follows: Cmax = 3.5 - 5.5 ng/mL; Tmax = 4- 12 hours. The pharmacokinetic parameters for ezetimibe-glucuronide are as follows: Cmax = 45 - 71 ng/mL; Tmax = 1-2 hours. Food has not impact on the extent of absorption of ezetimibe. However, Cmax increases by 38% with a high-fat meal.

Volume of distribution
Not Available
Protein binding

>90% bound to human plasma protein

Metabolism

Ezetimibe is primarily metabolized in the small intestine and liver via glucuronide conjugation (a phase II reaction) with subsequent biliary and renal excretion. In humans, ezetimibe is rapidly metabolized to ezetimibe-glucuronide.

Route of elimination

78% of the dose is excreted into feces. 11% of the dose is excreted into urine. Ezetimibe was the major component in feces and accounted for 69% of the administered dose, while ezetimibe-glucuronide was the major component in urine and accounted for 9% of the administered dose.

Half life

22 hours (both ezetimibe and ezetimibe-glucuronide).

Clearance
Not Available
Toxicity

The most common adverse reactions in the group of patients treated with ezetimibe that led to treatment discontinuation and occurred at a rate greater than placebo were, arthralgia (0.3%), dizziness (0.2%), and gamma-glutamyltransferase increase (0.2%).

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AtorvastatinThe risk or severity of adverse effects can be increased when Ezetimibe is combined with Atorvastatin.Approved
BezafibrateThe risk or severity of adverse effects can be increased when Bezafibrate is combined with Ezetimibe.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Ezetimibe.Approved, Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Ezetimibe.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Ezetimibe.Withdrawn
CholestyramineCholestyramine can cause a decrease in the absorption of Ezetimibe resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ColesevelamColesevelam can cause a decrease in the absorption of Ezetimibe resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
ColestipolColestipol can cause a decrease in the absorption of Ezetimibe resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Ezetimibe.Approved, Investigational, Vet Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Ezetimibe.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Ezetimibe.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Ezetimibe.Experimental
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Ezetimibe.Approved
EltrombopagThe serum concentration of Ezetimibe can be increased when it is combined with Eltrombopag.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Ezetimibe.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Ezetimibe.Approved
FenofibrateThe risk or severity of adverse effects can be increased when Fenofibrate is combined with Ezetimibe.Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Ezetimibe.Approved
GemfibrozilThe risk or severity of adverse effects can be increased when Gemfibrozil is combined with Ezetimibe.Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Ezetimibe.Approved, Investigational
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Ezetimibe.Approved, Investigational
LumacaftorThe serum concentration of Ezetimibe can be decreased when it is combined with Lumacaftor.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Ezetimibe.Illicit, Investigational, Withdrawn
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Ezetimibe.Experimental
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Ezetimibe.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Ezetimibe.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Ezetimibe.Experimental
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Ezetimibe.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Ezetimibe.Approved, Investigational, Vet Approved, Withdrawn
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Ezetimibe.Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Ezetimibe.Approved
RanolazineThe serum concentration of Ezetimibe can be increased when it is combined with Ranolazine.Approved, Investigational
RolapitantThe serum concentration of Ezetimibe can be increased when it is combined with Rolapitant.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Ezetimibe.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Ezetimibe.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Ezetimibe.Experimental
TeriflunomideThe serum concentration of Ezetimibe can be increased when it is combined with Teriflunomide.Approved
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Ezetimibe.Approved, Experimental
Food Interactions
  • Take without regard to meals.

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]
External Links
Human Metabolome Database
HMDB15108
KEGG Drug
D01966
PubChem Compound
150311
PubChem Substance
46507625
ChemSpider
132493
BindingDB
50371521
ChEBI
49040
ChEMBL
CHEMBL1138
Therapeutic Targets Database
DAP000717
PharmGKB
PA10816
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ezetimibe
ATC Codes
C10BA02 — Simvastatin and ezetimibeC10BA05 — Atorvastatin and ezetimibeC10AX09 — EzetimibeC10BA06 — Rosuvastatin and ezetimibe
AHFS Codes
  • 24:06.05 — Cholesterol Absorption Inhibitors
FDA label
Download (321 KB)
MSDS
Download (281 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Enrolling by InvitationPreventionAtherosclerosis1
0RecruitingTreatmentEndometrial Cancers1
0RecruitingTreatmentProstate Cancer1
1CompletedBasic ScienceCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Disorder of Cholesterol Metabolism / Dyslipidemias1
1CompletedBasic ScienceDrug Interactions / Hypercholesterolaemia / Immunosuppression / Pharmacokinetics2
1CompletedBasic ScienceDrug Interactions / Intestinal Transporter Expression / Pharmacodynamics / Pharmacokinetics1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHypercholesterolaemia1
1CompletedOtherHypercholesterolaemia1
1CompletedScreeningDyslipidemias1
1CompletedTreatmentAcute Kidney Injury (AKI)1
1CompletedTreatmentAlopecia Areata (AA)1
1CompletedTreatmentAtherosclerosis / Hypercholesterolaemia1
1CompletedTreatmentCholesterol1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHypercholesterolaemia1
1CompletedTreatmentHypercholesterolaemia / Hyperlipidemias1
1CompletedTreatmentHyperlipidemias1
1CompletedTreatmentPharmacokinetics1
1RecruitingBasic ScienceChronic Hepatitis C Virus (HCV) Infection1
2Active Not RecruitingTreatmentHepatitis D, Chronic1
2Active Not RecruitingTreatmentHypercholesterolaemia1
2CompletedDiagnosticHealthy Volunteers1
2CompletedDiagnosticType 2 Diabetes Mellitus1
2CompletedTreatmentDiabetes, Diabetes Mellitus Type 1 / Dyslipidemias1
2CompletedTreatmentDiabetic Polyneuropathy / Oxidative Stress1
2CompletedTreatmentDyslipidemias1
2CompletedTreatmentHypercholesterolaemia6
2CompletedTreatmentHyperlipidemias3
2CompletedTreatmentLipoidosis1
2CompletedTreatmentNon Alcoholic Steatohepatitis1
2Not Yet RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2TerminatedTreatmentNonalcoholic Fatty Liver Disease (NAFLD)1
2, 3CompletedTreatmentCoronary Artery Disease1
3Active Not RecruitingTreatmentAtherosclerosis / Hypercholesterolaemia / Statin Adverse Reaction1
3Active Not RecruitingTreatmentHypercholesterolaemia3
3Active Not RecruitingTreatmentHypercholesterolaemia / Hypercholesterolemia, Familial1
3CompletedDiagnosticCholesterol1
3CompletedPreventionAtherosclerosis / Hypercholesterolaemia / Hyperlipoproteinemia Type II1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Peripheral Arterial Disease (PAD)1
3CompletedTreatmentAtherosclerosis / Cardiovascular Disease (CVD)1
3CompletedTreatmentAtherosclerosis / Coronary Artery Disease / Hypercholesterolaemia1
3CompletedTreatmentAtherosclerosis / Coronary Heart Disease (CHD) / Hypercholesterolaemia2
3CompletedTreatmentAtherosclerosis / Hypercholesterolaemia1
3CompletedTreatmentCardiovascular Disorder / Diabetes Mellitus (DM)1
3CompletedTreatmentCombined (Atherogenic) Dyslipidemia / Coronary Heart Disease (CHD) / Dyslipidemias / Mixed hypercholesterolemia1
3CompletedTreatmentCoronary Heart Disease (CHD) / Hypercholesterolaemia4
3CompletedTreatmentCoronary Heart Disease (CHD) / Hypercholesterolaemia / Type 2 Diabetes Mellitus1
3CompletedTreatmentDyslipidemias1
3CompletedTreatmentDyslipidemias / Hypercholesterolaemia1
3CompletedTreatmentHeart Diseases / Lipid Metabolism, Inborn Errors3
3CompletedTreatmentHeart Diseases / Metabolism, Inborn Errors1
3CompletedTreatmentHypercholesterolaemia27
3CompletedTreatmentHypercholesterolaemia / Hyperlipidemias1
3CompletedTreatmentHypercholesterolaemia / Hypertriglyceridemias2
3CompletedTreatmentHypercholesterolaemia / Metabolic Syndromes1
3CompletedTreatmentHypercholesterolaemia / Myocardial Infarction (MI)1
3CompletedTreatmentHypercholesterolemia, Familial2
3CompletedTreatmentHyperlipidemia Combined1
3CompletedTreatmentHyperlipidemias5
3CompletedTreatmentMetabolic Syndromes1
3RecruitingTreatmentHypercholesterolaemia1
3RecruitingTreatmentHyperlipidemias1
3TerminatedBasic ScienceAtherosclerosis / Hypercholesterolaemia1
3TerminatedTreatmentCoronary Artery Disease / High Cholesterol1
3TerminatedTreatmentDyslipidemias / Hyperlipidemias1
3TerminatedTreatmentHypercholesterolaemia2
3TerminatedTreatmentHypercholesterolemia, Familial / Lipid Metabolism, Inborn Errors1
3TerminatedTreatmentHyperlipidemias1
3TerminatedTreatmentHypertensive1
3TerminatedTreatmentStable Coronary Artery Disease Undergoing PCI1
3Unknown StatusTreatmentHypercholesterolaemia1
3Unknown StatusTreatmentInflammatory Reaction1
4CompletedBasic ScienceAtherosclerosis1
4CompletedBasic ScienceDeficiency, Vitamin D1
4CompletedBasic ScienceHypercholesterolaemia1
4CompletedDiagnosticHealthy Men1
4CompletedDiagnosticST Segment Elevation Myocardial Infarction (STEMI)1
4CompletedHealth Services ResearchPeripheral Arterial Disease (PAD)1
4CompletedPreventionCardiovascular Disease (CVD)1
4CompletedPreventionHemostasis / Inflammatory Reaction / Magnetic Resonance Imaging (MRI) / Neuropsychology / Nonvalvular Atrial Fibrillation1
4CompletedPreventionKidney Disease, Chronic1
4CompletedPreventionMyocardial Infarction (MI)1
4CompletedTreatmentAtherosclerosis1
4CompletedTreatmentAtherosclerosis / Coronary Heart Disease (CHD) / Diabetes / Dyslipidemias / Strokes1
4CompletedTreatmentAtherosclerosis / Coronary Heart Disease (CHD) / Hypercholesterolaemia1
4CompletedTreatmentAtherosclerosis / Hypercholesterolaemia3
4CompletedTreatmentCardiovascular Disorder1
4CompletedTreatmentCoronary Arteriosclerosis / Hypercholesterolaemia1
4CompletedTreatmentCoronary Artery Disease / Diabetes1
4CompletedTreatmentCoronary Artery Disease / Hypercholesterolaemia1
4CompletedTreatmentCoronary Heart Disease (CHD)1
4CompletedTreatmentCoronary Heart Disease (CHD) / Hypercholesterolaemia2
4CompletedTreatmentDiabetes Mellitus (DM) / Impaired Renal Function1
4CompletedTreatmentDyslipidemias1
4CompletedTreatmentDyslipidemias / Transplanted1
4CompletedTreatmentHypercholesterolaemia16
4CompletedTreatmentHypercholesterolaemia / Hyperlipidemias1
4CompletedTreatmentHypercholesterolaemia / Type 2 Diabetes Mellitus1
4CompletedTreatmentHypercholesterolemia, Familial1
4CompletedTreatmentHyperlipidemias1
4CompletedTreatmentLipid Metabolism Disorders1
4CompletedTreatmentMetabolic Syndromes3
4CompletedTreatmentPostprandial Lipaemia / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentCoronary Artery Disease2
4Not Yet RecruitingTreatmentDiabetes Mellitus and Hypercholesterolemia1
4RecruitingPreventionCoronary Artery Disease1
4RecruitingTreatmentAcute Coronary Syndromes (ACS) / Hypercholesterolaemia1
4RecruitingTreatmentChronic Hepatitis C Infection1
4RecruitingTreatmentHypercholesterolaemia1
4RecruitingTreatmentType 2 Diabetes Mellitus1
4TerminatedTreatmentAtherosclerosis1
4TerminatedTreatmentAtherosclerosis / Coronary Artery Disease / Hypercholesterolaemia1
4TerminatedTreatmentAtherosclerosis / Hypercholesterolaemia1
4Unknown StatusNot AvailableCoronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Hypercholesterolaemia / Non-Coronary Atherosclerotic Disease1
4Unknown StatusTreatmentCoronary Artery Disease3
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections / Hyperlipidemias1
4Unknown StatusTreatmentHypercholesterolaemia1
4Unknown StatusTreatmentMetabolic Syndromes1
4Unknown StatusTreatmentType 2 Diabetes Mellitus Without Insulin Treatment1
4Unknown StatusTreatment•Non-alcoholic Steatohepatitis (NASH)1
4WithdrawnTreatmentCardiovascular Disease (CVD) / Hyperlipidemias1
4WithdrawnTreatmentDyslipidemias1
Not AvailableActive Not RecruitingBasic ScienceHomozygous Sitosterolemia1
Not AvailableActive Not RecruitingPreventionCoronary Heart Disease (CHD)1
Not AvailableCompletedNot AvailableCoronary Heart Disease (CHD) / Hypercholesterolaemia1
Not AvailableCompletedNot AvailableHomozygous Familial Hypercholesterolemia / Hypercholesterolemia, Familial1
Not AvailableCompletedNot AvailableHomozygous Sitosterolemia / Hypercholesterolaemia / Hypercholesterolemia, Familial2
Not AvailableCompletedNot AvailableHypercholesterolaemia2
Not AvailableCompletedNot AvailableHypercholesterolaemia / Hyperlipidemias1
Not AvailableCompletedHealth Services ResearchHypercholesterolaemia1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / Coronary Artery Disease / Metabolic Syndromes1
Not AvailableCompletedTreatmentCardiovascular Risks / Hypercholesterolaemia / Inflammatory Reaction / Pre-Diabetic1
Not AvailableCompletedTreatmentCholesterol, LDL1
Not AvailableCompletedTreatmentDyslipidemias1
Not AvailableCompletedTreatmentEndothelial Dysfunction1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Hypercholesterolaemia1
Not AvailableCompletedTreatmentPeripheral Artery Disease (PAD)1
Not AvailableCompletedTreatmentStable Angina (SA)1
Not AvailableRecruitingNot AvailableDyslipidemias / Type 2 Diabetes Mellitus1
Not AvailableUnknown StatusNot AvailableEndothelial Function1
Not AvailableUnknown StatusNot AvailableHeterozigous Familial Hypercholesterolemia1
Not AvailableUnknown StatusBasic ScienceAcute Coronary Syndromes (ACS)1
Not AvailableWithdrawnBasic ScienceChronic Acalculous Cholecystitis1
Not AvailableWithdrawnTreatmentAtherosclerosis1

Pharmacoeconomics

Manufacturers
  • Msp singapore co llc
Packagers
Dosage forms
FormRouteStrength
TabletOral10 mg
Tablet, film coatedOral
TabletOral
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)
US5846966No1993-09-212013-09-21Us
US5969156Yes1997-01-082017-01-08Us
USRE37721Yes1997-04-252017-04-25Us
USRE42461Yes1997-04-252017-04-25Us
US7612058Yes2006-04-302026-04-30Us
US7030106Yes2002-07-252022-07-25Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)163°C FDA label
water solubilityInsoluble FDA label
logP4.5Not Available
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
Polarizability41.64 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

Taxonomy

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
Monobactam / 1-phenylazetidine / 2-phenylazetidine / 1-hydroxy-2-unsubstituted benzenoid / Fluorobenzene / Halobenzene / Phenol / Aryl fluoride / Aryl halide / Monocyclic benzene moiety
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, azetidines, beta-lactam (CHEBI:49040)

Targets

Kind
Protein
Organism
Human
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
Human
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
Human
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
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. 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
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. 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
Human
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
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. 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
Human
Pharmacological action
Unknown
Actions
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. 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]

Transporters

Kind
Protein
Organism
Human
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
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein heterodimerization activity
Specific Function
Transporter that appears to play an indispensable role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile.
Gene Name
ABCG5
Uniprot ID
Q9H222
Uniprot Name
ATP-binding cassette sub-family G member 5
Molecular Weight
72503.02 Da
References
  1. Couture P, Lamarche B: Ezetimibe and bile acid sequestrants: impact on lipoprotein metabolism and beyond. Curr Opin Lipidol. 2013 Jun;24(3):227-32. doi: 10.1097/MOL.0b013e3283613a55. [PubMed:23571732]
Kind
Protein
Organism
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sterol transporter activity
Specific Function
Transporter that appears to play an indispensable role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile.
Gene Name
ABCG8
Uniprot ID
Q9H221
Uniprot Name
ATP-binding cassette sub-family G member 8
Molecular Weight
75678.03 Da
References
  1. Couture P, Lamarche B: Ezetimibe and bile acid sequestrants: impact on lipoprotein metabolism and beyond. Curr Opin Lipidol. 2013 Jun;24(3):227-32. doi: 10.1097/MOL.0b013e3283613a55. [PubMed:23571732]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:34