U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H38O5
Molecular Weight 418.5662
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SIMVASTATIN

SMILES

CCC(C)(C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@@H]12

InChI

InChIKey=RYMZZMVNJRMUDD-HGQWONQESA-N
InChI=1S/C25H38O5/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3/t15-,16-,18+,19+,20-,21-,23-/m0/s1

HIDE SMILES / InChI
Molecular Formula C25H38O5
Molecular Weight 418.5662
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/simvastatin.html http://www.rxlist.com/zocor-drug.htm http://www.wikidoc.org/index.php/Simvastatin

Simvastatin is a HMG-CoA Reductase Inhibitor that is FDA approved for the treatment of hypercholesterolemia and for the reduction in the risk of cardiac heart disease mortality and cardiovascular events. It reduces levels of "bad" cholesterol (low-density lipoprotein, or LDL) and triglycerides in the blood, while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL). Common adverse reactions include abdominal pain, constipation, nausea, headache, upper respiratory infection. Cases of myopathy/rhabdomyolysis have been observed with simvastatin co-administered with lipid-modifying doses ( ≥ 1 g/day niacin) of niacin-containing products. The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine.

CNS Activity

Originator

Merck
238
Curator's Comment: # Merck & Co., Inc.

Approval Year

1991
122
Targets

Targets

Primary TargetPharmacologyConditionPotency
Solute carrier organic anion transporter family member 3A1
6
Target ID: Q9UIG8
Gene ID: 28232.0
Gene Symbol: SLCO3A1
Target Organism: Homo sapiens (Human)
Binding Agent
1076
Solute carrier organic anion transporter family member 1B1
32
Target ID: Q9Y6L6
Gene ID: 10599.0
Gene Symbol: SLCO1B1
Target Organism: Homo sapiens (Human)
Binding Agent
1076
3-hydroxy-3-methylglutaryl-coenzyme A reductase
9
Target ID: P04035
Gene ID: 3156.0
Gene Symbol: HMGCR
Target Organism: Homo sapiens (Human)
Inhibitor
8504
Substrate
661
Inhibitor
8504
 4.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Approved
8583
ZOCOR

Approved Use

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin tablets, USP can be started simultaneously with diet. Simvastatin tablets, USP are an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce the risk of total mortality by reducing CHD deaths and reduce the risk of non-fatal myocardial infarction, stroke, and the need for revascularization procedures in patients at high risk of coronary events. (1.1) Reduce elevated total-C, LDL-C, Apo B, TG and increase HDL-C in patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia. (1.2) Reduce elevated TG in patients with hypertriglyceridemia and reduce TG and VLDL-C in patients with primary dysbeta­lipoproteinemia. (1.2) Reduce total-C and LDL-C in adult patients with homozygous familial hypercholesterolemia. (1.2) Reduce elevated total-C, LDL-C, and Apo B in boys and postmenarchal girls, 10 to 17 years of age with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy. (1.2, 1.3) Limitations of Use Simvastatin tablets, USP have not been studied in Fredrickson Types I and V dyslipidemias. (1.4) 1.1 Reductions in Risk of CHD Mortality and Cardiovascular Events In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, simvastatin tablets, USP are indicated to: Reduce the risk of total mortality by reducing CHD deaths. Reduce the risk of non-fatal myocardial infarction and stroke. Reduce the need for coronary and non-coronary revascularization procedures. 1.2 Hyperlipidemia Simvastatin tablets, USP are indicated to: Reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIb). Reduce elevated TG in patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia). Reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia). Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. 1.3 Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFH) Simvastatin tablets, USP are indicated as an adjunct to diet to reduce total-C, LDL-C, and Apo B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with HeFH, if after an adequate trial of diet therapy the following findings are present: 1. LDL cholesterol remains ≥190 mg/dL; or 2. LDL cholesterol remains ≥160 mg/dL and There is a positive family history of premature cardiovascular disease (CVD) or Two or more other CVD risk factors are present in the adolescent patient. The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C <130 mg/dL. The optimal age at which to initiate lipid-lowering therapy to decrease the risk of symptomatic adulthood CAD has not been determined. 1.4 Limitations of Use Simvastatin tablets, USP have not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).

Launch Date

1991
Primary
Approved
8583
ZOCOR

Approved Use

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin tablets, USP can be started simultaneously with diet. Simvastatin tablets, USP are an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce the risk of total mortality by reducing CHD deaths and reduce the risk of non-fatal myocardial infarction, stroke, and the need for revascularization procedures in patients at high risk of coronary events. (1.1) Reduce elevated total-C, LDL-C, Apo B, TG and increase HDL-C in patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia. (1.2) Reduce elevated TG in patients with hypertriglyceridemia and reduce TG and VLDL-C in patients with primary dysbeta­lipoproteinemia. (1.2) Reduce total-C and LDL-C in adult patients with homozygous familial hypercholesterolemia. (1.2) Reduce elevated total-C, LDL-C, and Apo B in boys and postmenarchal girls, 10 to 17 years of age with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy. (1.2, 1.3) Limitations of Use Simvastatin tablets, USP have not been studied in Fredrickson Types I and V dyslipidemias. (1.4) 1.1 Reductions in Risk of CHD Mortality and Cardiovascular Events In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, simvastatin tablets, USP are indicated to: Reduce the risk of total mortality by reducing CHD deaths. Reduce the risk of non-fatal myocardial infarction and stroke. Reduce the need for coronary and non-coronary revascularization procedures. 1.2 Hyperlipidemia Simvastatin tablets, USP are indicated to: Reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIb). Reduce elevated TG in patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia). Reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia). Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. 1.3 Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFH) Simvastatin tablets, USP are indicated as an adjunct to diet to reduce total-C, LDL-C, and Apo B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with HeFH, if after an adequate trial of diet therapy the following findings are present: 1. LDL cholesterol remains ≥190 mg/dL; or 2. LDL cholesterol remains ≥160 mg/dL and There is a positive family history of premature cardiovascular disease (CVD) or Two or more other CVD risk factors are present in the adolescent patient. The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C <130 mg/dL. The optimal age at which to initiate lipid-lowering therapy to decrease the risk of symptomatic adulthood CAD has not been determined. 1.4 Limitations of Use Simvastatin tablets, USP have not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).

Launch Date

1991
Primary
Approved
8583
ZOCOR

Approved Use

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin tablets, USP can be started simultaneously with diet. Simvastatin tablets, USP are an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce the risk of total mortality by reducing CHD deaths and reduce the risk of non-fatal myocardial infarction, stroke, and the need for revascularization procedures in patients at high risk of coronary events. (1.1) Reduce elevated total-C, LDL-C, Apo B, TG and increase HDL-C in patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia. (1.2) Reduce elevated TG in patients with hypertriglyceridemia and reduce TG and VLDL-C in patients with primary dysbeta­lipoproteinemia. (1.2) Reduce total-C and LDL-C in adult patients with homozygous familial hypercholesterolemia. (1.2) Reduce elevated total-C, LDL-C, and Apo B in boys and postmenarchal girls, 10 to 17 years of age with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy. (1.2, 1.3) Limitations of Use Simvastatin tablets, USP have not been studied in Fredrickson Types I and V dyslipidemias. (1.4) 1.1 Reductions in Risk of CHD Mortality and Cardiovascular Events In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, simvastatin tablets, USP are indicated to: Reduce the risk of total mortality by reducing CHD deaths. Reduce the risk of non-fatal myocardial infarction and stroke. Reduce the need for coronary and non-coronary revascularization procedures. 1.2 Hyperlipidemia Simvastatin tablets, USP are indicated to: Reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIb). Reduce elevated TG in patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia). Reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia). Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable. 1.3 Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFH) Simvastatin tablets, USP are indicated as an adjunct to diet to reduce total-C, LDL-C, and Apo B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with HeFH, if after an adequate trial of diet therapy the following findings are present: 1. LDL cholesterol remains ≥190 mg/dL; or 2. LDL cholesterol remains ≥160 mg/dL and There is a positive family history of premature cardiovascular disease (CVD) or Two or more other CVD risk factors are present in the adolescent patient. The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C <130 mg/dL. The optimal age at which to initiate lipid-lowering therapy to decrease the risk of symptomatic adulthood CAD has not been determined. 1.4 Limitations of Use Simvastatin tablets, USP have not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).

Launch Date

1991
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
6.85 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01960140
40 mg single, oral
dose: 40 mg
route of administration: oral
experiment type: single
co-administered:
SIMVASTATIN plasma
Homo sapiens
population: healthy
age:
sex:
food status:
1.93 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01960140
40 mg single, oral
dose: 40 mg
route of administration: oral
experiment type: single
co-administered:
TENIVASTATIN plasma
Homo sapiens
population: healthy
age:
sex:
food status:
5.006 ng/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01979185
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
SIMVASTATIN plasma
Homo sapiens
population: healthy
age: Adults
sex:
food status:
54.711 ng/mL
REVIEW
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206679Orig1s000ClinPharmR.pdf
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMVASTATIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
38.142 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01979185
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
SIMVASTATIN plasma
Homo sapiens
population: healthy
age: Adults
sex:
food status:
34.351 ng*h/mL
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01979185
20 mg single, oral
dose: 20 mg
route of administration: oral
experiment type: single
co-administered:
SIMVASTATIN plasma
Homo sapiens
population: healthy
age: Adults
sex:
food status:
235.795 ng × h/mL
REVIEW
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206679Orig1s000ClinPharmR.pdf
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMVASTATIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.87 h
REVIEW
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206679Orig1s000ClinPharmR.pdf
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMVASTATIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

inhibitor
2252
substrate
1193

inhibitor
2438
substrate
1388

inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
BSEP
550

CYP2C8
1057

CYP2C19
2057

P-gp
1741
CYP3A5
446

CYP2A6
626

CYP2C8
810

CYP2C19
1119

CYP1A2
1197

CYP2E1
729

OATP2
11

OATP1B1
503

OATP1B3
435
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
2633
 moderate [Ki 10 uM]
CYP2C8
1117
 moderate [Ki 7.1 uM]
CYP2C9
2497
 moderate
CYP2D6
2546
 moderate
CYP2C19
2141
 no
P-gp
1932
 yes [IC50 9 uM]
BSEP
554
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1946
 major
yes (co-administration study)
Comment: cyclosporine has been shown to increase the AUC of statins. The increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4
CYP3A5
446
 minor
CYP1A2
1197
 no
CYP2A6
626
 no
CYP2C19
1119
 no
CYP2C8
810
 no
CYP2C9
1193
 no
CYP2D6
1388
 no
CYP2E1
729
 no
OATP1B3
435
 yes
OATP2
11
 yes
OATP1B1
503
 yes
yes (co-administration study)
Comment: Administered with cyclosporine: AUC of Simvastatin increased 2.6 fold
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:9150
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9150
eMolecules
11021557
https://www.emolecules.com/cgi-bin/more?vid=11021557
eMolecules
2724261
https://www.emolecules.com/cgi-bin/more?vid=2724261
eMolecules
36754543
https://www.emolecules.com/cgi-bin/more?vid=36754543
MolPort
MolPort-002-507-345
https://www.molport.com/shop/molecule-link/MolPort-002-507-345
Selleck Chemicals
Simvastatin(Zocor)
http://www.selleckchem.com/products/Simvastatin(Zocor).html
ZINC
ZINC000003780893
http://zinc15.docking.org/substances/ZINC000003780893
PubMed

PubMed

TitleDatePubMed
The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition.
2017-04
Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin.
2005-08
3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors block calcium-dependent tyrosine kinase Pyk2 activation by angiotensin II in vascular endothelial cells. involvement of geranylgeranylation of small G protein Rap1.
2001-05-11
An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia.
2001-05
Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.
2001-04-17
Differential effect of simvastatin on various signal transduction intermediates in cultured human smooth muscle cells.
2001-04-15
Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia.
2001-04-01
Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice.
2001-04
A new simvastatin (mevinolin)-resistance marker from Haloarcula hispanica and a new Haloferax volcanii strain cured of plasmid pHV2.
2001-04
Clinical and biochemical features, molecular diagnosis and long-term management of a case of cerebrotendinous xanthomatosis.
2001-04
LpAI in HDL subfractions: serum levels in men and women with coronary heart disease and changes under hypolipemic therapy.
2001-04
Rhabdomyolysis due to simvastatin in a transplant patient: Are some statins safer than others?
2001-04
Comparative study of HMG-CoA reductase inhibitors on fibrinogen.
2001-04
Safety and efficacy of simvastatin for hyperlipidemia in renal transplant recipients: a double-blind, randomized, placebo-controlled study.
2001-03-27
Pro and con: low-density lipoprotein cholesterol lowering is and will be the key to the future of lipid management.
2001-03-08
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.
2001-03-08
Magnetic resonance detects changes in phosphocholine associated with Ras activation and inhibition in NIH 3T3 cells.
2001-03-02
Effect of simvastatin in preventing progression of carotid artery stenosis.
2001-03-01
Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators.
2001-03-01
[Treatment with statins for the reduction of cardiovascular risk].
2001-03
High-dose simvastin (80 mg/day) decreases plasma concentrations of total homocyst(e)ine in patients with hypercholesteromia.
2001-03
Statin-fibrate combinations in patients with combined hyperlipedemia.
2001-03
Statin therapy--what now?
2001-03
The influence of short-term treatment with simvastatin on the inflammatory profile of patients with hypercholesterolaemia.
2001-03
Effect of simvastatin on vascular smooth muscle responsiveness: involvement of Ca(2+) homeostasis.
2001-03
Making the most of cholesterol-lowering margarines.
2001-03
Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration.
2001-03
HMG-CoA reductase inhibitors and P-glycoprotein modulation.
2001-03
Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia.
2001-03
Simvastatin improves arterial compliance in the lower limb but not in the aorta.
2001-03
Effects of simvastatin treatment on sICAM-1 and sE-selectin levels in hypercholesterolemic subjects.
2001-03
Sildenafil-simvastatin interaction: possible cause of rhabdomyolysis?
2001-02-15
Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease.
2001-02
Clinical relevance of statins: their role in secondary prevention.
2001-02
Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin.
2001-02
The effects of lacidipine on the steady/state plasma concentrations of simvastatin in healthy subjects.
2001-02
Treatment with simvastatin and low-dose aspirin depresses thrombin generation in patients with coronary heart disease and borderline-high cholesterol levels.
2001-02
[Statins: intervention studies, facts and perspectives].
2001-02
Do HMG-CoA reductase inhibitors affect fibrinogen?
2001-02
The HMG-CoA reductase inhibitor simvastatin inhibits IFN-gamma induced MHC class II expression in human vascular endothelial cells.
2001-01-27
[The role of HDL in the prevention of cardiovascular events].
2001-01-21
Effective use of statins to prevent coronary heart disease.
2001-01-15
Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis.
2001-01
[Cost-effectiveness of atorvastatin against simvastatin as hypolipemic treatment in hypercholesterolemic patients in primary care].
2001-01
Hypolipidemic effect of NK-104 and other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in guinea pigs.
2001-01
Simvastatin: building on success.
2001-01
Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.
2001-01
[Antioxidative effects of fluvastatin, and its major metabolites [II]].
2001-01
Cost effectiveness of HMG-CoA reductase inhibition in Canada.
2001
Advantages of lipid-lowering therapy in cerebral ischemia: role of HMG-CoA reductase inhibitors.
2001
Patents

Patents

07175854
29
EP 33538
6
JP2001507331A
6
JP2002145770A
6
JP2002501887A
14
JP2002543189A
7
JP2003515526A
470
JP2005200419A
6
JP2006335658A
9
JP2006512417A
10
JP2006521825A
7
JP2007500677A
22
JP2007529285A
16
JP2008539832A
84
JP2009235105A
7
JP2009511496A
7
JP2009521905A
7
JP2009536078A
7
JP2010090094A
15
JP2010150288A
7
JP2011510067A
60
JP2011524897A
9
JP2011525181A
8
JP2011529067A
37
JP4078300B2
6
JP4708327B2
54
JP4832303B2
14
JP4833840B2
20
JPH0334934A
7
US 4444784
6

Sample Use Guides

In Vivo Use Guide
Unknown
Route of Administration: Unknown
In Vitro Use Guide
The pleiotropic effects and uptake of simvastatin acid were analyzed in primary human cardiomyocytes and HEK293 cells transfected with the OATP3A1 (Human organic anion transporting polypeptide 3A1) gene. It was observed a pH-dependent effect on OATP3A1 uptake, with more efficient simvastatin acid uptake at pH5.5 in HEK293 cells transfected with the OATP3A1 gene. The Michaelis-Menten constant (Km) for simvastatin acid uptake by OATP3A1 was 0.017±0.002μM and the Vmax was 0.995±0.027fmol/min/105 cells. Uptake of simvastatin acid was significantly increased by known (benzylpenicillin and estrone-3-sulfate) and potential (indoxyl sulfate and cyclosporine) substrates of OATP3A1.
Substance Class Chemical
Created
by admin
on Wed Apr 02 09:08:40 GMT 2025
Edited
by admin
on Wed Apr 02 09:08:40 GMT 2025
Record UNII
AGG2FN16EV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
C10AA01
Preferred Name English
SIMVASTATIN
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
SIMVASTATIN [MI]
Common Name English
SIMVASTATIN [JAN]
Common Name English
MK-0733
Code English
ZOCOR
Brand Name English
simvastatin [INN]
Common Name English
SIMVASTATIN [EP MONOGRAPH]
Common Name English
SIMCOR COMPONENT SIMVASTATIN
Common Name English
SIMVASTATIN [MART.]
Common Name English
SIMVASTATIN [USP MONOGRAPH]
Common Name English
SYNVINOLIN
Common Name English
SIMVASTATIN [ORANGE BOOK]
Common Name English
2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-[2-[(1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl]ethyl]tetrahydro-4-hydroxy-2H-pyran-2-one
Common Name English
VYTORIN COMPONENT SIMVASTATIN
Common Name English
NSC-758706
Code English
SIMVASTATIN [VANDF]
Common Name English
MK-733
Code English
SIMVASTATIN [HSDB]
Common Name English
Simvastatin [WHO-DD]
Common Name English
SIMVASTATIN [USAN]
Common Name English
POLYCAP COMPONENT SIMVASTATIN
Brand Name English
BUTANOIC ACID, 2,2-DIMETHYL-, 1,2,3,7,8,8A-HEXAHYDRO-3,7-DIMETHYL-8-(2-(TETRAHYDRO-4-HYDROXY-6-OXO-2H-PYRAN-2-YL)ETHYL)-1-NAPHTHALENYL ESTER, (1S-(1.ALPHA.,3.ALPHA.,7.BETA.,8.BETA.(2S*,4S*),8A.BETA.))-
Common Name English
SIMVASTATIN [USP-RS]
Common Name English
Classification Tree Code System Code
WHO-ATC C10BX04
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-ATC C10BA04
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-VATC QC10BA04
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
NCI_THESAURUS C1655
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-ATC A10BH51
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
NDF-RT N0000175589
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
LIVERTOX NBK548720
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-VATC QC10BA02
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-VATC QC10AA01
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-VATC QA10BH51
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-ATC C10BA02
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
NDF-RT N0000000121
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-ATC C10AA01
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-VATC QC10BX01
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-ATC C10BX01
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-ESSENTIAL MEDICINES LIST 12.6
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
WHO-VATC QC10BX04
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
Code System Code Type Description
DAILYMED
AGG2FN16EV
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
EPA CompTox
DTXSID0023581
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
HSDB
7208
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
LACTMED
Simvastatin
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
ChEMBL
CHEMBL1064
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
NCI_THESAURUS
C29454
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
USAN
Y-41
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
INN
6147
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
RS_ITEM_NUM
1612700
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
MERCK INDEX
m9947
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY Merck Index
MESH
D019821
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
CHEBI
9150
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
CAS
79902-63-9
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
WIKIPEDIA
SIMVASTATIN
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
DRUG BANK
DB00641
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
EVMPD
SUB10529MIG
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
DRUG CENTRAL
2445
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
FDA UNII
AGG2FN16EV
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
PUBCHEM
54454
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
RXCUI
36567
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY RxNorm
NSC
758706
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
SMS_ID
100000091786
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
IUPHAR
2955
Created by admin on Wed Apr 02 09:08:41 GMT 2025 , Edited by admin on Wed Apr 02 09:08:41 GMT 2025
PRIMARY
Related Record Type Details
Structure of SIMVASTATIN
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
OATP1B1
TRANSPORTER -> SUBSTRATE
CYTOCHROME P450 3A5
METABOLIC ENZYME -> SUBSTRATE
OATP-B
TRANSPORTER -> INHIBITOR
Structure of SIMVASTATIN
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
EP
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
OCT-1
TRANSPORTER -> INHIBITOR
OAT-1
TRANSPORTER -> INHIBITOR
OAT-3
TRANSPORTER -> INHIBITOR
Related Record Type Details
Structure of 6-HYDROXYSIMVASTATIN, (6S)-
METABOLITE ACTIVE -> PARENT
Structure of Dimebutic Acid
METABOLITE -> PARENT
PLASMA
Structure of TENIVASTATIN
METABOLITE ACTIVE -> PRODRUG
MAJOR
Structure of 6-EXOMETHYLENESIMVASTATIN
METABOLITE ACTIVE -> PARENT
MAJOR
Structure of 3-HYDROXYSIMVASTATIN
METABOLITE ACTIVE -> PARENT
MAJOR
Related Record Type Details
Structure of SIMVASTATIN DIMER
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of TENIVASTATIN
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of LOVASTATIN
IMPURITY -> PARENT
sum of impurities E and F: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of SIMVASTATIN DIMER
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of METHYLENE SIMVASTATIN
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of TENIVASTATIN
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of EPILOVASTATIN
IMPURITY -> PARENT
sum of impurities E and F: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of METHYLENE SIMVASTATIN
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of LOVASTATIN
IMPURITY -> PARENT
Epilovastatin and Lovastatin 1.0%
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of EPILOVASTATIN
IMPURITY -> PARENT
Epilovastatin and Lovastatin 1.0%
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of ACETYL SIMVASTATIN
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of ANHYDRO SIMVASTATIN
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of ANHYDRO SIMVASTATIN
IMPURITY -> PARENT
sum of impurities B and C: not more than 1.6 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.8 per cent);
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of ACETYL SIMVASTATIN
IMPURITY -> PARENT
sum of impurities B and C: not more than 1.6 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.8 per cent);
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
Structure of TENIVASTATIN
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SIMVASTATIN ACID
PHARMACOKINETIC
Tmax PHARMACOKINETIC
ORAL BIOAVAILABILITY PHARMACOKINETIC
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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