Identification

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

Ezetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and related phytosterol absorption. The discovery and research of this drug began in the early 1990's, where intravenous administration of radio-labelled compound in rats resulting in subsequent localization of the drug within enterocytes at the intestinal villus, leading to studies of investigating the effect of ezetimibe on intestinal cholesterol absorption [3]. Ezetimibe is used as an adjunctive therapy to diet to lower cholesterol levels in primary hyperlipidemia, mixed hyperlipidemia, homozygous familial hypercholesterolemia (HoFH), and homozygous sitosterolemia (phytosterolemia) [Label].

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 the first drug that does not affect 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 the mice were insensitive to ezetimibe treatment [3]. Based on these findings, it is indicated 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 [Label].

Structure
Thumb
Synonyms
  • Ezedoc
  • Ezetimiba
  • Ezetimibum
  • Ezetrol
External IDs
MK0653 / SCH-58235 / SCH58235
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act EzetimibeTablet10 mgOralActavis Pharma Company2014-09-15Not applicableCanada
EzetimibeTablet10 mgOralPro Doc Limitee2014-09-17Not applicableCanada
EzetimibeTablet10 mgOralSivem Pharmaceuticals Ulc2014-09-16Not applicableCanada
EzetimibeTablet10 mgOralSanis Health Inc2014-10-08Not applicableCanada
EzetrolTablet10 mgOralMerck Ltd.2003-06-15Not applicableCanada
Gln-ezetimibeTablet10 mgOralGlenmark Pharmaceuticals, IncNot applicableNot applicableCanada
M-ezetimibeTablet10 mgOralMantra Pharma Inc2017-12-14Not applicableCanada
Sandoz EzetimibeTablet10 mgOralSandoz Canada Incorporated2014-09-15Not applicableCanada
ZetiaTablet10 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2012-03-192018-03-30Us
ZetiaTablet10 mg/1OralA S Medication Solutions2002-10-25Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ach-ezetimibeTablet10 mgOralAccord Healthcare Limited2014-09-17Not applicableCanada
Apo-ezetimibeTablet10 mgOralApotex Corporation2014-09-23Not applicableCanada
Auro-ezetimibeTablet10 mgOralAuro Pharma IncNot applicableNot applicableCanada
Bio-ezetimibeTablet10 mgOralBiomed Pharma2014-10-08Not applicableCanada
EzetimibeTablet10 mg/1OralSandoz2017-06-12Not applicableUs
EzetimibeTablet10 mg/1OralGlenmark Pharmaceuticals Inc.,Usa2011-12-31Not applicableUs
EzetimibeTablet10 mg/1OralAv Pak2017-07-02Not applicableUs
EzetimibeTablet10 mg/1OralAv Kare, Inc.2017-06-15Not applicableUs
EzetimibeTablet10 mg/1OralMajor2017-06-12Not applicableUs
EzetimibeTablet10 mg/1OralAmneal Pharmaceuticals2017-06-12Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 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 (80 mg/1)Tablet, film coatedOralImpax Generics2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (40 mg/1)TabletOralActavis Pharma Company2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (10 mg/1)Tablet, film coatedOralImpax Generics2017-04-26Not applicableUs
Ezetimibe and SimvastatinEzetimibe (10 mg/1) + Simvastatin (20 mg/1)TabletOralA S Medication Solutions2017-04-26Not 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 (20 mg/1)TabletOralAmneal Pharmaceuticals2017-11-21Not 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 (40 mg/1)Tablet, film coatedOralImpax Generics2017-04-26Not applicableUs
International/Other Brands
Ezedoc / Ezetib / Zetia / Zient
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[C@@H](CC[C@@H]1[C@H](N(C1=O)C1=CC=C(F)C=C1)C1=CC=C(O)C=C1)C1=CC=C(F)C=C1

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), reduce elevated total-C, LDL-C, Apo B, and non-HDL-C in patients with mixed hyperlipidemia in combination with fenofibrate, reduce elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH), in combination with atorvastatin or simvastatin, and to reduce elevated sitosterol and campesterol in patients with homozygous sitosterolemia (phytosterolemia) [Label].

Associated Conditions
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 [Label]. This therapeutic effect was more profound when ezetimibe was co-administered with a statin or fenofibrate compared to either treatment alone [Label]. 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].

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 at the enterocyte/ 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 can bind to the sterol-sensing domain of NPC1L1 and form a NPC1L1/cholesterol complex. The complex can then be 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, a 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 proteins complexes involved in regulating cholesterol uptake, including the CAV1– annexin 2 heterocomplex [2].

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

Administration of a single 10-mg dose of ezetimibe in fasted adults resulted in a peak plasma concentrations (Cmax) of 3.4 to 5.5 ng/mL were achieved within 4 to 12 hours (Tmax) [Label]. The Cmax of the major pharmacologically-active metabolite, ezetimibe-glucuronide, was 45 to 71 ng/mL and the Tmax was between 1 and 2 hours [Label]. Food consumption had minimal effect on ezetimibe absorption, but the Cmax was increased by 38% with consumption of high-fat meals [Label]. The absolute bioavailability of ezetimibe cannot be determined, as the compound is virtually insoluble in aqueous media suitable for injection [Label].

Volume of distribution

The relative volume of distribution of ezetimibe is 107.5L [5].

Protein binding

Ezetimibe and ezetimibe-glucuronide are >90% bound to human plasma proteins [Label]. 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 glucuronidating 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 [Label]. In humans, ezetimibe and ezetimibe-glucuronide constitutes approximately 93% of the total drug in plasma [Label]. Plasma concentration-time profiles exhibit multiple peaks, suggesting enterohepatic recycling [Label], and about 20% of the drug distributed is reabsorbed due to enterohepatic re-circulation [5].

Route of elimination

Following oral administration, about 78% and 11% of the administered radio-labelled ezetimibe were recovered in the feces and urine, respectively [Label]. Ezetimibe was the major component in feces and accounted for 69% of the administered dose as unconjugated compound, while ezetimibe-glucuronide was the major component in urine and accounted for 9% of the administered dose [Label]. 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 [Label].

Clearance

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

Toxicity

Oral LD50 and intraperitoneal LD50 in rat were >2000 mg/kg [MSDS]. Estimated oral LD50 values in mouse and dog are >5000 mg/kg and >3000 mg/kg, respectively [MSDS]. 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 [Label]. In case of overdose, symptomatic treatment is recommended [Label].

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Ezetimibe can be increased when it is combined with Acetaminophen.Approved
AmiodaroneThe serum concentration of Ezetimibe can be increased when it is combined with Amiodarone.Approved, Investigational
AmlodipineThe serum concentration of Ezetimibe can be increased when it is combined with Amlodipine.Approved
ApalutamideThe serum concentration of Ezetimibe can be decreased when it is combined with Apalutamide.Approved, Investigational
AsunaprevirThe serum concentration of Asunaprevir can be increased when it is combined with Ezetimibe.Approved, Investigational, Withdrawn
AtorvastatinThe risk or severity of adverse effects can be increased when Ezetimibe is combined with Atorvastatin.Approved
Benzyl alcoholThe serum concentration of Ezetimibe can be increased when it is combined with Benzyl alcohol.Approved
BepridilThe serum concentration of Ezetimibe can be increased when it is combined with Bepridil.Approved, Withdrawn
BezafibrateThe risk or severity of adverse effects can be increased when Bezafibrate is combined with Ezetimibe.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it 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
CaffeineThe serum concentration of Ezetimibe can be increased when it is combined with Caffeine.Approved
CarbamazepineThe serum concentration of Ezetimibe can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Ezetimibe can be increased when it is combined with Carvedilol.Approved, Investigational
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Ezetimibe.Approved, Withdrawn
CholestyramineCholestyramine can cause a decrease in the absorption of Ezetimibe resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Investigational
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
DexniguldipineThe serum concentration of Ezetimibe can be increased when it is combined with Dexniguldipine.Experimental
DexverapamilThe serum concentration of Ezetimibe can be increased when it is combined with Dexverapamil.Experimental
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.Approved, 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, Investigational
DiltiazemThe serum concentration of Ezetimibe can be increased when it is combined with Diltiazem.Approved, Investigational
DoxazosinThe serum concentration of Ezetimibe can be increased when it is combined with Doxazosin.Approved
EltrombopagThe serum concentration of Ezetimibe can be increased when it is combined with Eltrombopag.Approved
EmopamilThe serum concentration of Ezetimibe can be increased when it is combined with Emopamil.Experimental
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
EstradiolThe excretion of Ezetimibe can be decreased when combined with Estradiol.Approved, Investigational, Vet Approved
Ethinyl EstradiolThe serum concentration of Ezetimibe can be decreased when it is combined with Ethinyl Estradiol.Approved
FelodipineThe serum concentration of Ezetimibe can be increased when it is combined with Felodipine.Approved, Investigational
FenofibrateThe risk or severity of adverse effects can be increased when Fenofibrate is combined with Ezetimibe.Approved
FentanylThe serum concentration of Ezetimibe can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FluoxetineThe serum concentration of Ezetimibe can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe serum concentration of Ezetimibe can be increased when it is combined with Fluvoxamine.Approved, Investigational
GallopamilThe serum concentration of Ezetimibe can be increased when it is combined with Gallopamil.Investigational
GemfibrozilThe risk or severity of adverse effects can be increased when Gemfibrozil is combined with Ezetimibe.Approved
GlyburideThe serum concentration of Glyburide can be increased when it is combined with Ezetimibe.Approved
GlycerinThe serum concentration of Ezetimibe can be increased when it is combined with Glycerin.Approved, Investigational
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Ezetimibe.Approved
IbuprofenThe serum concentration of Ezetimibe can be increased when it is combined with Ibuprofen.Approved
IrinotecanThe serum concentration of Irinotecan can be increased when it is combined with Ezetimibe.Approved, Investigational
IsavuconazoleThe serum concentration of Ezetimibe can be increased when it is combined with Isavuconazole.Approved, Investigational
IsradipineThe serum concentration of Ezetimibe can be increased when it is combined with Isradipine.Approved, Investigational
LamivudineThe serum concentration of Lamivudine can be increased when it is combined with Ezetimibe.Approved, Investigational
LamotrigineThe serum concentration of Ezetimibe can be decreased when it is combined with Lamotrigine.Approved, Investigational
LidocaineThe serum concentration of Ezetimibe can be increased when it is combined with Lidocaine.Approved, Vet Approved
LipegfilgrastimEzetimibe may increase the myelosuppressive activities of Lipegfilgrastim.Approved, Investigational
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Ezetimibe.Approved, Investigational
LomerizineThe serum concentration of Ezetimibe can be increased when it is combined with Lomerizine.Experimental
LoperamideThe serum concentration of Ezetimibe can be increased when it is combined with Loperamide.Approved
LoratadineThe serum concentration of Ezetimibe can be increased when it is combined with Loratadine.Approved, Investigational
LosartanThe serum concentration of Ezetimibe can be increased when it is combined with Losartan.Approved
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
MibefradilThe serum concentration of Ezetimibe can be increased when it is combined with Mibefradil.Investigational, Withdrawn
MiconazoleThe serum concentration of Ezetimibe can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
NicardipineThe serum concentration of Ezetimibe can be increased when it is combined with Nicardipine.Approved, Investigational
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Ezetimibe.Approved, Investigational
NiguldipineThe serum concentration of Ezetimibe can be increased when it is combined with Niguldipine.Experimental
NimodipineThe serum concentration of Ezetimibe can be increased when it is combined with Nimodipine.Approved, Investigational
NisoldipineThe serum concentration of Ezetimibe can be increased when it is combined with Nisoldipine.Approved
NitrendipineThe serum concentration of Ezetimibe can be increased when it is combined with Nitrendipine.Approved, Investigational
NystatinThe excretion of Ezetimibe can be decreased when combined with Nystatin.Approved, Vet Approved
OmeprazoleThe serum concentration of Ezetimibe can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
ParoxetineThe serum concentration of Ezetimibe can be increased when it is combined with Paroxetine.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Ezetimibe.Approved, Investigational, Vet Approved, Withdrawn
PhenobarbitalThe serum concentration of Ezetimibe can be decreased when it is combined with Phenobarbital.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Ezetimibe.Approved
PitolisantThe serum concentration of Ezetimibe can be decreased when it is combined with Pitolisant.Approved, Investigational
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Ezetimibe.Approved
PromethazineThe serum concentration of Ezetimibe can be increased when it is combined with Promethazine.Approved, Investigational
PropafenoneThe serum concentration of Ezetimibe can be increased when it is combined with Propafenone.Approved
RanitidineThe serum concentration of Ezetimibe can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Ezetimibe can be increased when it is combined with Ranolazine.Approved, Investigational
RifampicinThe serum concentration of Ezetimibe can be decreased when it is combined with Rifampicin.Approved
RilpivirineThe serum concentration of Rilpivirine can be increased when it is combined with Ezetimibe.Approved
RolapitantThe serum concentration of Ezetimibe can be increased when it is combined with Rolapitant.Approved, Investigational
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
SulfasalazineThe serum concentration of Sulfasalazine 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
TetrandrineThe serum concentration of Ezetimibe can be increased when it is combined with Tetrandrine.Experimental
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Ezetimibe.Approved
VemurafenibThe serum concentration of Ezetimibe can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe serum concentration of Ezetimibe can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Ezetimibe can be increased when it is combined with Verapamil.Approved
ZidovudineThe serum concentration of Ezetimibe can be decreased when it is combined with Zidovudine.Approved
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]
  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. 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
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 (350 KB)
MSDS
Download (281 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceCoronary Heart Disease (CHD) / High Blood Cholesterol Level1
0Enrolling by InvitationPreventionAtherosclerosis1
0RecruitingTreatmentEndometrial Cancers1
0RecruitingTreatmentProstate Cancer1
1CompletedBasic ScienceCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Disorder of Cholesterol Metabolism / Dyslipidemias1
1CompletedBasic ScienceDrug Interactions / High Blood Cholesterol Level / Immunosuppression / Pharmacokinetics2
1CompletedBasic ScienceDrug Interactions / Intestinal Transporter Expression / Pharmacodynamics / Pharmacokinetics1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHigh Blood Cholesterol Level1
1CompletedOtherHigh Blood Cholesterol Level1
1CompletedScreeningDyslipidemias1
1CompletedTreatmentAcute Kidney Injury (AKI)1
1CompletedTreatmentAlopecia Areata (AA)1
1CompletedTreatmentAtherosclerosis / High Blood Cholesterol Level1
1CompletedTreatmentCholesterol1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHigh Blood Cholesterol Level1
1CompletedTreatmentHigh Blood Cholesterol Level / Hyperlipidemias1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHyperlipidemias1
1CompletedTreatmentPharmacokinetics1
1Not Yet RecruitingTreatmentHealthy Male Volunteers1
1RecruitingBasic ScienceChronic Hepatitis C Virus (HCV) Infection1
2Active Not RecruitingTreatmentHepatitis D, Chronic1
2Active Not RecruitingTreatmentHigh Blood Cholesterol Level1
2CompletedDiagnosticHealthy Volunteers1
2CompletedDiagnosticType 2 Diabetes Mellitus1
2CompletedTreatmentDiabetes, Diabetes Mellitus Type 1 / Dyslipidemias1
2CompletedTreatmentDiabetic Polyneuropathy / Oxidative Stress1
2CompletedTreatmentDyslipidemias1
2CompletedTreatmentHigh Blood Cholesterol Level6
2CompletedTreatmentHyperlipidemias3
2CompletedTreatmentLipoidosis1
2CompletedTreatmentNon Alcoholic Steatohepatitis1
2RecruitingTreatmentCholesterolemia / Diabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
2RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2TerminatedTreatmentNonalcoholic Fatty Liver Disease (NAFLD)1
2, 3CompletedTreatmentCoronary Artery Disease1
3Active Not RecruitingTreatmentHigh Blood Cholesterol Level1
3CompletedDiagnosticCholesterol1
3CompletedPreventionAtherosclerosis / High Blood Cholesterol Level / 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 / High Blood Cholesterol Level1
3CompletedTreatmentAtherosclerosis / Coronary Heart Disease (CHD) / High Blood Cholesterol Level2
3CompletedTreatmentAtherosclerosis / High Blood Cholesterol Level1
3CompletedTreatmentAtherosclerosis / High Blood Cholesterol Level / Statin Adverse Reaction1
3CompletedTreatmentCardiovascular Disorder / Diabetes Mellitus (DM)1
3CompletedTreatmentCombined (Atherogenic) Dyslipidemia / Coronary Heart Disease (CHD) / Dyslipidemias / Mixed hypercholesterolemia1
3CompletedTreatmentCoronary Heart Disease (CHD) / High Blood Cholesterol Level4
3CompletedTreatmentCoronary Heart Disease (CHD) / High Blood Cholesterol Level / Type 2 Diabetes Mellitus1
3CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa)2
3CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa) / High Blood Cholesterol Level1
3CompletedTreatmentDyslipidemias1
3CompletedTreatmentDyslipidemias / High Blood Cholesterol Level1
3CompletedTreatmentHeart Diseases / Lipid Metabolism, Inborn Errors3
3CompletedTreatmentHeart Diseases / Metabolism, Inborn Errors1
3CompletedTreatmentHigh Blood Cholesterol Level28
3CompletedTreatmentHigh Blood Cholesterol Level / Hyperlipidemias1
3CompletedTreatmentHigh Blood Cholesterol Level / Hypertriglyceridemias2
3CompletedTreatmentHigh Blood Cholesterol Level / Metabolic Syndromes1
3CompletedTreatmentHigh Blood Cholesterol Level / Myocardial Infarction1
3CompletedTreatmentHyperlipidemia Combined1
3CompletedTreatmentHyperlipidemias6
3CompletedTreatmentMetabolic Syndromes1
3Not Yet RecruitingTreatmentHigh Blood Cholesterol Level1
3RecruitingTreatmentHigh Blood Cholesterol Level2
3RecruitingTreatmentHyperlipidemias1
3TerminatedBasic ScienceAtherosclerosis / High Blood Cholesterol Level1
3TerminatedTreatmentCoronary Artery Disease / High Blood Cholesterol Level1
3TerminatedTreatmentDyslipidemia (Fredrickson Type Ⅱa) / Lipid Metabolism, Inborn Errors1
3TerminatedTreatmentDyslipidemias / Hyperlipidemias1
3TerminatedTreatmentHigh Blood Cholesterol Level2
3TerminatedTreatmentHigh Blood Pressure (Hypertension)1
3TerminatedTreatmentHyperlipidemias1
3TerminatedTreatmentStable Coronary Artery Disease Undergoing PCI1
3Unknown StatusTreatmentHigh Blood Cholesterol Level1
3Unknown StatusTreatmentInflammatory Reaction1
4Active Not RecruitingTreatmentAcute Coronary Syndromes (ACS) / High Blood Cholesterol Level1
4CompletedBasic ScienceAtherosclerosis1
4CompletedBasic ScienceDeficiency, Vitamin D1
4CompletedBasic ScienceHigh Blood Cholesterol Level1
4CompletedDiagnosticHealthy Men1
4CompletedDiagnosticST Segment Elevation Myocardial Infarction (STEMI)1
4CompletedHealth Services ResearchPeripheral Arterial Disease (PAD)1
4CompletedPreventionCardiovascular Disease (CVD)1
4CompletedPreventionChronic Kidney Disease (CKD)1
4CompletedPreventionHemostasis / Inflammatory Reaction / Magnetic Resonance Imaging (MRI) / Neuropsychology / Nonvalvular Atrial Fibrillation1
4CompletedPreventionMyocardial Infarction1
4CompletedTreatmentAtherosclerosis1
4CompletedTreatmentAtherosclerosis / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Dyslipidemias / Strokes1
4CompletedTreatmentAtherosclerosis / Coronary Heart Disease (CHD) / High Blood Cholesterol Level1
4CompletedTreatmentAtherosclerosis / High Blood Cholesterol Level3
4CompletedTreatmentCardiovascular Disorder1
4CompletedTreatmentCoronary Arteriosclerosis / High Blood Cholesterol Level1
4CompletedTreatmentCoronary Artery Disease / Diabetes Mellitus (DM)1
4CompletedTreatmentCoronary Artery Disease / High Blood Cholesterol Level1
4CompletedTreatmentCoronary Heart Disease (CHD)1
4CompletedTreatmentCoronary Heart Disease (CHD) / High Blood Cholesterol Level2
4CompletedTreatmentDiabetes Mellitus (DM) / Impaired Renal Function1
4CompletedTreatmentDyslipidemia (Fredrickson Type Ⅱa)1
4CompletedTreatmentDyslipidemias1
4CompletedTreatmentDyslipidemias / Transplanted1
4CompletedTreatmentHigh Blood Cholesterol Level16
4CompletedTreatmentHigh Blood Cholesterol Level / Hyperlipidemias1
4CompletedTreatmentHigh Blood Cholesterol Level / Type 2 Diabetes Mellitus1
4CompletedTreatmentHyperlipidemias1
4CompletedTreatmentLipid Metabolism Disorders1
4CompletedTreatmentMetabolic Syndromes3
4CompletedTreatmentPostprandial Lipaemia / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentCoronary Artery Disease2
4RecruitingPreventionCoronary Artery Disease1
4RecruitingTreatmentChronic Kidney Disease (CKD) / High Blood Cholesterol Level1
4RecruitingTreatmentDiabetes Mellitus and Hypercholesterolemia1
4RecruitingTreatmentHepatitis C Viral Infection1
4RecruitingTreatmentHigh Blood Cholesterol Level1
4RecruitingTreatmentType 2 Diabetes Mellitus1
4TerminatedTreatmentAtherosclerosis1
4TerminatedTreatmentAtherosclerosis / Coronary Artery Disease / High Blood Cholesterol Level1
4TerminatedTreatmentAtherosclerosis / High Blood Cholesterol Level1
4Unknown StatusNot AvailableCoronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Cholesterol Level / Non-Coronary Atherosclerotic Disease1
4Unknown StatusTreatmentCoronary Artery Disease3
4Unknown StatusTreatmentHigh Blood Cholesterol Level1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections / Hyperlipidemias1
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) / High Blood Cholesterol Level1
Not AvailableCompletedNot AvailableDyslipidemia (Fredrickson Type Ⅱa) / High Blood Cholesterol Level / Homozygous Sitosterolemia2
Not AvailableCompletedNot AvailableDyslipidemia (Fredrickson Type Ⅱa) / Homozygous Familial Hypercholesterolemia1
Not AvailableCompletedNot AvailableHigh Blood Cholesterol Level2
Not AvailableCompletedNot AvailableHigh Blood Cholesterol Level / Hyperlipidemias1
Not AvailableCompletedHealth Services ResearchHigh Blood Cholesterol Level1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / Coronary Artery Disease / Metabolic Syndromes1
Not AvailableCompletedTreatmentCardiovascular Risks / High Blood Cholesterol Level / Inflammatory Reaction / Pre-Diabetic1
Not AvailableCompletedTreatmentCholesterol, LDL1
Not AvailableCompletedTreatmentDyslipidemias1
Not AvailableCompletedTreatmentEndothelial Dysfunction1
Not AvailableCompletedTreatmentHigh Blood Cholesterol Level / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentPeripheral Artery Disease (PAD)1
Not AvailableCompletedTreatmentStable Angina (SA)1
Not AvailableRecruitingNot AvailableDyslipidemias / Type 2 Diabetes Mellitus1
Not AvailableRecruitingBasic ScienceAtherosclerosis / Cardiovascular Disease (CVD)1
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
  • 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
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
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
Curator comments
In vitro of human liver microsomes, the IC50 value was 7 μmol/L.
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
Human
Pharmacological action
Unknown
Curator comments
According to an in vitro assay, the IC50 value was 31 μmol/L in human liver microsomes.
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]

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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on August 15, 2018 09:47