SIMVASTATIN

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 Search

SMILES

[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]3C[C@@H](O)CC(=O)O3)OC(=O)C(C)(C)CC

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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28350522 | https://www.ncbi.nlm.nih.gov/pubmed/28887287http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
Solute carrier organic anion transporter family member 3A1 6 Target ID: Q9UIG8 Gene ID: 28232.0 Gene Symbol: SLCO3A1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28887287	Binding Agent 1059
Solute carrier organic anion transporter family member 1B1 32 Target ID: Q9Y6L6 Gene ID: 10599.0 Gene Symbol: SLCO1B1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/28350522	Binding Agent 1059
3-hydroxy-3-methylglutaryl-coenzyme A reductase 7 Target ID: P04035 Gene ID: 3156.0 Gene Symbol: HMGCR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12827636	Inhibitor 8228
Cytochrome P450 3A4 126 Target ID: CHEMBL340 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Substrate 656
HMG-CoA reductase 46 Target ID: CHEMBL402 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Inhibitor 8228	4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2565
Coronary heart disease mortality and cardiovascular events 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Preventing	Approved 8360	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 6.9344638E11
Hyperlipidemia 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Primary	Approved 8360	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 6.9344638E11
Homozygous and heterozygous familial hypercholesterolemia 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Primary	Approved 8360	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 6.9344638E11

C_max

Value	Dose	Analyte	Population
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
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:
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:

AUC

Value	Dose	Analyte	Population
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
34.3509999999999 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:
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:

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inhibitor 1579	substrate 1010 inhibitor 1752	substrate 1193 inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 401 CYP2C8 901 CYP2C19 1463 P-gp 1437	CYP3A5 391 CYP2A6 523 CYP2C8 688 CYP2C19 985 CYP1A2 1032 CYP2E1 648 OATP2 11 OATP1B1 403 OATP1B3 347

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1909	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/ \| https://pubmed.ncbi.nlm.nih.gov/8737761/	moderate [Ki 10 uM]
CYP2C8 955	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/15998357/ \| https://pubmed.ncbi.nlm.nih.gov/15601807/ \| https://pubmed.ncbi.nlm.nih.gov/9321523/	moderate [Ki 7.1 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/8737761/ \| https://pubmed.ncbi.nlm.nih.gov/9321523/	moderate
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/ \| https://pubmed.ncbi.nlm.nih.gov/8737761/	moderate
CYP2C19 1537	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/11474784/	yes [IC50 9 uM]
BSEP 402	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/24014644/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019766s085lbl.pdf	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 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/ \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019766s085lbl.pdf
CYP3A5 391	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	minor
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2A6 523	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2C8 688	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
OATP1B3 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24989890/	yes
OATP2 11	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10601278/	yes
OATP1B1 403	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/19785645/ \| https://pubmed.ncbi.nlm.nih.gov/24989890/	yes	yes (co-administration study) Comment: Administered with cyclosporine: AUC of Simvastatin increased 2.6 fold Sources: https://pubmed.ncbi.nlm.nih.gov/19785645/ \| https://pubmed.ncbi.nlm.nih.gov/24989890/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://pubmed.ncbi.nlm.nih.gov/21525004/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9150	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9150
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
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

PubMed

Title	Date	PubMed
Advantages of lipid-lowering therapy in cerebral ischemia: role of HMG-CoA reductase inhibitors.	2001	11244205
Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice.	2001 Apr	11283400
A new simvastatin (mevinolin)-resistance marker from Haloarcula hispanica and a new Haloferax volcanii strain cured of plasmid pHV2.	2001 Apr	11283291
Clinical and biochemical features, molecular diagnosis and long-term management of a case of cerebrotendinous xanthomatosis.	2001 Apr	11282095
LpAI in HDL subfractions: serum levels in men and women with coronary heart disease and changes under hypolipemic therapy.	2001 Apr	11282093
Rhabdomyolysis due to simvastatin in a transplant patient: Are some statins safer than others?	2001 Apr	11274299
Comparative study of HMG-CoA reductase inhibitors on fibrinogen.	2001 Apr	11254918
Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia.	2001 Apr 1	11286949
Differential effect of simvastatin on various signal transduction intermediates in cultured human smooth muscle cells.	2001 Apr 15	11286990
Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.	2001 Apr 17	11306519
Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease.	2001 Feb	11293560
Clinical relevance of statins: their role in secondary prevention.	2001 Feb	11286152
Myositis, microvesicular hepatitis, and progression to cirrhosis from troglitazone added to simvastatin.	2001 Feb	11281188
The effects of lacidipine on the steady/state plasma concentrations of simvastatin in healthy subjects.	2001 Feb	11259986
Treatment with simvastatin and low-dose aspirin depresses thrombin generation in patients with coronary heart disease and borderline-high cholesterol levels.	2001 Feb	11246536
[Statins: intervention studies, facts and perspectives].	2001 Feb	11240416
Do HMG-CoA reductase inhibitors affect fibrinogen?	2001 Feb	11215845
Sildenafil-simvastatin interaction: possible cause of rhabdomyolysis?	2001 Feb 15	11237079
Safety and efficacy of simvastatin for hyperlipidemia in renal transplant recipients: a double-blind, randomized, placebo-controlled study.	2001 Feb-Mar	11267254
Protective effects of fluvastatin against reactive oxygen species induced DNA damage and mutagenesis.	2001 Jan	11234994
[Cost-effectiveness of atorvastatin against simvastatin as hypolipemic treatment in hypercholesterolemic patients in primary care].	2001 Jan	11218969
Hypolipidemic effect of NK-104 and other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in guinea pigs.	2001 Jan	11215324
Simvastatin: building on success.	2001 Jan	11211458
Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.	2001 Jan	11204586
[Antioxidative effects of fluvastatin, and its major metabolites [II]].	2001 Jan	11201159
Effective use of statins to prevent coronary heart disease.	2001 Jan 15	11201696
[The role of HDL in the prevention of cardiovascular events].	2001 Jan 21	11217160
The HMG-CoA reductase inhibitor simvastatin inhibits IFN-gamma induced MHC class II expression in human vascular endothelial cells.	2001 Jan 27	11219190
[Treatment with statins for the reduction of cardiovascular risk].	2001 Mar	11307779
High-dose simvastin (80 mg/day) decreases plasma concentrations of total homocyst(e)ine in patients with hypercholesteromia.	2001 Mar	11293393
Statin-fibrate combinations in patients with combined hyperlipedemia.	2001 Mar	11293392
Statin therapy--what now?	2001 Mar	11284361
The influence of short-term treatment with simvastatin on the inflammatory profile of patients with hypercholesterolaemia.	2001 Mar	11281303
Effect of simvastatin on vascular smooth muscle responsiveness: involvement of Ca(2+) homeostasis.	2001 Mar	11275002
Making the most of cholesterol-lowering margarines.	2001 Mar	11263847
Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration.	2001 Mar	11254756
HMG-CoA reductase inhibitors and P-glycoprotein modulation.	2001 Mar	11250868
Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia.	2001 Mar	11230791
Simvastatin improves arterial compliance in the lower limb but not in the aorta.	2001 Mar	11223448
Effects of simvastatin treatment on sICAM-1 and sE-selectin levels in hypercholesterolemic subjects.	2001 Mar	11223435
Effect of simvastatin in preventing progression of carotid artery stenosis.	2001 Mar 1	11230855
Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators.	2001 Mar 1	11230838
Magnetic resonance detects changes in phosphocholine associated with Ras activation and inhibition in NIH 3T3 cells.	2001 Mar 2	11237392
Pro and con: low-density lipoprotein cholesterol lowering is and will be the key to the future of lipid management.	2001 Mar 8	11256850
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.	2001 Mar 8	11256847
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 May	11303007
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 May 11	11278472
Cost effectiveness of HMG-CoA reductase inhibition in Canada.	2001 Spring	11283756
Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin.	2005 Aug	15901796
The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition.	2017 Apr	28350522

Patents

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 `Thu Jul 06 22:50:35 UTC 2023` Edited by `admin` on `Thu Jul 06 22:50:35 UTC 2023`
Record UNII	AGG2FN16EV
Record Status	`Validated (UNII)`
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Name

Type

Language

SIMVASTATIN

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 COMPONENT OF SIMCOR

Common Name

English

SIMVASTATIN [EP MONOGRAPH]

Common Name

English

C10AA01

Code

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

SIMVASTATIN COMPONENT OF VYTORIN

Common Name

English

Classification Tree Code System Code

WHO-ATC

C10BX04