TENIVASTATIN CALCIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C25H39O6.Ca
Molecular Weight	911.225
Optical Activity	UNSPECIFIED
Defined Stereocenters	14 / 14
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Ca++].[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H](O)C[C@@H](O)CC([O-])=O)OC(=O)C(C)(C)CC.[H][C@]34[C@H](C[C@@H](C)C=C3C=C[C@H](C)[C@@H]4CC[C@@H](O)C[C@@H](O)CC([O-])=O)OC(=O)C(C)(C)CC

InChI

InChIKey=FGHWDPOUOIKHKK-XQOMDNQHSA-L

InChI=1S/2C25H40O6.Ca/c2*1-6-25(4,5)24(30)31-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-18(26)13-19(27)14-22(28)29;/h2*7-8,11,15-16,18-21,23,26-27H,6,9-10,12-14H2,1-5H3,(H,28,29);/q;;+2/p-2/t2*15-,16-,18+,19+,20-,21-,23-;/m00./s1

HIDE SMILES / InChI

Molecular Formula	Ca
Molecular Weight	40.078
Charge	2
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C25H39O6
Molecular Weight	435.5736
Charge	-1
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	0
Optical Activity	UNSPECIFIED

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

Tenivastatin (well known as simvastatin acid or simvastatin hydroxy acid) is a pharmacologically active metabolite, which is formed in the mammalian organism from lactone prodrug, simvastatin. Tenivastatin is a potent reversible inhibitor of HMGCR (HMG-CoA reductase), reduces cholesterol synthesis and increases low-density lipoprotein (LDL) receptors on cell membranes of liver and extrahepatic tissues. It is also a substrate of organic anion transporting polypeptide 1B1 (OATP1B1/Oatp2), an influx transporter expressed on the sinusoidal membrane of hepatocytes. Recent studies have shown that OATP1B1 plays a clinically important role in the hepatic elimination of several drugs including statins, via mediating the hepatic uptake. In addition, was discovered, that the tenivastatin was a substrate of another transporter protein, human organic anion transporting polypeptide 3A1 (OATP3A1), which is predominately expressed in the heart. Presence of OATP3A1 in cardiomyocytes suggested that transporter could modulate the exposure of cardiac tissue to simvastatin acid due to its enrichment in cardiomyocytes. Increases in the uptake of simvastatin acid by OATP3A1 when combined with OATP substrates suggest the potential for drug-drug interactions that could influence clinical outcomes.

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 1064
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 1064
3-hydroxy-3-methylglutaryl-coenzyme A reductase 9 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 8297
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Substrate 661
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Inhibitor 8297	4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2578
Coronary heart disease mortality and cardiovascular events 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Preventing	Approved 8429	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
Hyperlipidemia 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Primary	Approved 8429	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
Homozygous and heterozygous familial hypercholesterolemia 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019766s093lbl.pdf	Primary	Approved 8429	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

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 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 402 CYP2C8 911 CYP2C19 1478 P-gp 1461	CYP3A5 395 CYP2A6 543 CYP2C8 693 CYP2C19 991 CYP1A2 1054 CYP2E1 667 OATP2 11 OATP1B1 406 OATP1B3 350

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/ \| https://pubmed.ncbi.nlm.nih.gov/8737761/	moderate [Ki 10 uM]
CYP2C8 965	inhibitor 3277 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 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/8737761/ \| https://pubmed.ncbi.nlm.nih.gov/9321523/	moderate
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/ \| https://pubmed.ncbi.nlm.nih.gov/8737761/	moderate
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11474784/	yes [IC50 9 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24014644/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 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 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	minor
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9321523/	no
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24989890/	yes
OATP2 11	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10601278/	yes
OATP1B1 406	substrate 3367 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 1647	inhibitor 1626 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
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
Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia.	2001 Feb	11182189
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
Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin.	2001 Jan	11197581
How cost-effective is the treatment of dyslipidemia in patients with diabetes but without cardiovascular disease?	2001 Jan	11194239
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
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
A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro.	2001 Mar	11181496
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

Patents

Sample Use Guides

In Vivo Use Guide

Dose range is 5 to 40 mg/day. Recommended usual starting dose is 10 or 20 mg once a day in the evening (for patients at high risk of Coronary heart defect is 40 mg/day). Due to the increased risk of myopathy, including rhabdomyolysis, use of the 80-mg dose of Simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.

Route of Administration: Oral

In Vitro Use Guide

Simvastatin (30 μM) significantly (P <0.01) inhibited the proliferative effect of H2O2 (0.5 mM) and its stimulatory actions on ERK1/2 phosphorylation, NF-κB activation and IL-8 production.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:50:55 GMT 2023` Edited by `admin` on `Fri Dec 15 15:50:55 GMT 2023`
Record UNII	YNO268EI8T
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TENIVASTATIN CALCIUM

Official Name

English

TENIVASTATIN CALCIUM [USP-RS]

Common Name

English

Calcium (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-(2,2-dimethylbutyryloxy)-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate (1:2)

Common Name

English

TENIVASTATIN CALCIUM [USAN]

Common Name

English

1-NAPHTHALENEHEPTANOIC ACID, 8-(2,2-DIMETHYL-1-OXOBUTOXY)-1,2,6,7,8,8A-HEXAHYDRO-.BETA.,.DELTA.-DIHYDROXY-2,6-DIMETHYL-, CALCIUM SALT, (2:1), (.BETA.R,.DELTA.R,1S,2S,6R,8S,8AR)-

Common Name

English

Tenivastatin calcium [WHO-DD]

Common Name

English

L-654969

Code

English

L 654969

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1655