Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C24H21F2NO3 |
Molecular Weight | 409.4252 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O[C@@H](CC[C@@H]1[C@H](N(C1=O)C2=CC=C(F)C=C2)C3=CC=C(O)C=C3)C4=CC=C(F)C=C4
InChI
InChIKey=OLNTVTPDXPETLC-XPWALMASSA-N
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
DescriptionSources: http://www.drugbank.ca/drugs/DB00973Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/ezetimibe.html
Sources: http://www.drugbank.ca/drugs/DB00973
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/ezetimibe.html
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. 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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL2027 Sources: http://www.drugbank.ca/drugs/DB00973 |
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Target ID: CHEMBL2782 Sources: http://www.drugbank.ca/drugs/DB00973 |
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Target ID: CHEMBL5161 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18063367 |
200.0 nM [Ki] | ||
Target ID: CHEMBL612877 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27600041 |
30.0 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | ZETIA Approved UseEzetimibe, administered alone, is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia. Launch Date2002 |
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Primary | ZETIA Approved UseHomozygous Familial Hypercholesterolemia (HoFH)
The combination of Ezetimibe and atorvastatin or simvastatin is indicated for the reduction of elevated total-C and LDL-C levels in patients with HoFH, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. Launch Date2002 |
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Primary | ZETIA Approved UseEzetimibe is indicated as adjunctive therapy to diet for the reduction of elevated sitosterol and campesterol levels in patients with homozygous familial sitosterolemia. Launch Date2002 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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64.2 ng/mL |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
EZETIMIBE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
70.1 ng/mL |
10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
EZETIMIBE unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
3.4 ng/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
EZETIMIBE unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
726 ng × h/mL |
20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered: |
EZETIMIBE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
743 ng × h/mL |
10 mg 1 times / day multiple, oral dose: 10 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
EZETIMIBE unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10% |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
EZETIMIBE unknown | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, 57 years n = 1 Health Status: unhealthy Age Group: 57 years Sex: M Population Size: 1 Sources: |
Disc. AE: Liver injury... AEs leading to discontinuation/dose reduction: Liver injury Sources: |
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, children n = 92 Health Status: unhealthy Condition: Primary hypercholesterolemia Age Group: children Population Size: 92 Sources: |
Other AEs: Epilepsy congenital, Appendicitis... Other AEs: Epilepsy congenital (serious, 1 patient) Sources: Appendicitis (serious, 1 patient) Upper respiratory tract infection (below serious, 7 patients) |
50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: |
unhealthy n = 15 Health Status: unhealthy Population Size: 15 Sources: |
|
10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy n = 75 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 75 Sources: |
Other AEs: Cataract, Abdominal pain upper... Other AEs: Cataract (serious, 1 patient) Sources: Abdominal pain upper (serious, 1 patient) Type 2 diabetes mellitus (below serious, 7 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Liver injury | Disc. AE | 10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, 57 years n = 1 Health Status: unhealthy Age Group: 57 years Sex: M Population Size: 1 Sources: |
Upper respiratory tract infection | below serious, 7 patients | 10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, children n = 92 Health Status: unhealthy Condition: Primary hypercholesterolemia Age Group: children Population Size: 92 Sources: |
Appendicitis | serious, 1 patient | 10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, children n = 92 Health Status: unhealthy Condition: Primary hypercholesterolemia Age Group: children Population Size: 92 Sources: |
Epilepsy congenital | serious, 1 patient | 10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy, children n = 92 Health Status: unhealthy Condition: Primary hypercholesterolemia Age Group: children Population Size: 92 Sources: |
Type 2 diabetes mellitus | below serious, 7 patients | 10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy n = 75 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 75 Sources: |
Abdominal pain upper | serious, 1 patient | 10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy n = 75 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 75 Sources: |
Cataract | serious, 1 patient | 10 mg 1 times / day steady, oral Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: |
unhealthy n = 75 Health Status: unhealthy Condition: Type 2 Diabetes Population Size: 75 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
not significant | unlikely (co-administration study) Comment: administered using cocktail approach: caffeine, tolbutamide, dextromethorphan, IV midazolam, and dapsone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=19 Page: 19.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=18 Page: 18.0 |
yes [IC50 0.25 uM] | |||
Page: 11.0 |
yes [IC50 2.2 uM] | unlikely Comment: page 8: R-value extrapolation indicate potential for DDI as unlikely Page: 11.0 |
||
Page: 11.0 |
yes [IC50 2.9 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=18 Page: 18.0 |
yes [IC50 24 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=18 Page: 18.0 |
no | |||
yes | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=18 Page: 18.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=18 Page: 18.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=18 Page: 18.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21445_Zetia_biopharmr_P1.pdf#page=18 Page: 18.0 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Cholesterol absorption inhibition: a strategy for cholesterol-lowering therapy. | 2001 Dec |
|
Ezetimibe, a potent cholesterol absorption inhibitor, inhibits the development of atherosclerosis in ApoE knockout mice. | 2001 Dec |
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Ezetimibe (Schering-Plough). | 2001 Mar |
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[Statins remain the standard. New methods for lipid lowering therapy]. | 2001 Oct 18 |
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Gateways to Clinical Trials. | 2002 Apr |
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Future outlook: changing perspectives on best practice. | 2002 Feb |
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State of the art in cholesterol management: targeting multiple pathways. | 2002 Feb |
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Synthesis of fluorescent biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors. | 2002 Feb 11 |
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Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors. | 2002 Feb 11 |
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[Ezetimib. A new cholesterol absorption inhibitor]. | 2002 Jul |
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Selective cholesterol absorption inhibition: a novel strategy in lipid-lowering management. | 2002 Mar |
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Gateways to clinical trials. | 2002 Nov |
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[Ezetimib plus statin combination. A strong duo]. | 2002 Nov 28 |
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Ezetimibe in hypercholesterolaemia. | 2002 Oct |
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Promising therapies for cholesterol reduction. | 2002 Sep |
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Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. | 2003 Apr |
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Efficacy and safety of ezetimibe coadministered with pravastatin in patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. | 2003 Apr |
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New drug joins cholesterol-fighting arsenal. | 2003 Apr |
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Synthesis of a biotin-tagged photoaffinity probe of 2-azetidinone cholesterol absorption inhibitors. | 2003 Apr 17 |
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[Lowering cholesterol becomes easier. Combining instead of increasing dosage]. | 2003 Jan 23 |
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Ezetimibe added to ongoing statin therapy reduced LDL cholesterol in primary hypercholesterolemia. | 2003 Jul-Aug |
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Evaluation of the efficacy, safety, and tolerability of ezetimibe in primary hypercholesterolaemia: a pooled analysis from two controlled phase III clinical studies. | 2003 Jun |
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New cholesterol-lowering drug makes its mark. | 2003 Mar |
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New lipid-modifying therapies. | 2003 Mar |
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Gateways to clinical trials. | 2003 May |
|
[Coronary disease prevention: only the inhibition of inflammation is important. Why lower lipids, too?]. | 2003 May 22 |
|
The intestinal absorption of biliary and dietary cholesterol as a drug target for lowering the plasma cholesterol level. | 2003 Winter |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/ezetimibe.html
10 mg orally once a day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26167075
10uM/L ezetimibe treatment of Huh7 hepatocytes significantly decreased PA-induced fat accumulation and increased PA-reduced mRNA and protein expression involved in autophagy
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000008553
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WHO-ATC |
C10BA05
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WHO-VATC |
QC10AX09
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WHO-VATC |
QC10BA06
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WHO-ATC |
C10BA06
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WHO-ATC |
C10BA02
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WHO-ATC |
C10AX09
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WHO-VATC |
QC10BA05
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NCI_THESAURUS |
C29703
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WHO-VATC |
QC10BA02
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LIVERTOX |
NBK548095
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NDF-RT |
N0000175911
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EOR26LQQ24
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8010
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EOR26LQQ24
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C47529
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1269028
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ZETIA
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PRIMARY | APPROVE APRIL 2007 | ||
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150311
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m5228
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SUB16430MIG
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163222-33-1
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CHEMBL1138
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100000091598
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7737
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DB00973
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Ezetimibe
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1125
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DTXSID1044223
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N0000008553
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PRIMARY | Decreased Cholesterol Absorption [PE] | ||
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341248
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LL-18
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EZETIMIBE
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6816
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758923
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49040
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C108606
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)