Identification

Name
Simvastatin
Accession Number
DB00641
Description

Simvastatin, also known as the brand name product Zocor, is a lipid-lowering drug derived synthetically from a fermentation product of Aspergillus terreus. It belongs to the statin class of medications, which are used to lower the risk of cardiovascular disease and manage abnormal lipid levels by inhibiting the endogenous production of cholesterol in the liver. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase,2 which catalyzes the conversion of HMG-CoA to mevalonic acid and is the third step in a sequence of metabolic reactions involved in the production of several compounds involved in lipid metabolism and transport including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as "bad cholesterol"), and very low-density lipoprotein (VLDL). Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD, such as those with Type 2 Diabetes. The clear evidence of the benefit of statin use coupled with very minimal side effects or long term effects has resulted in this class becoming one of the most widely prescribed medications in North America.3,4

Simvastatin and other drugs from the statin class of medications including atorvastatin, pravastatin, rosuvastatin, fluvastatin, and lovastatin are considered first-line options for the treatment of dyslipidemia.3,4 Increasing use of the statin class of drugs is largely due to the fact that cardiovascular disease (CVD), which includes heart attack, atherosclerosis, angina, peripheral artery disease, and stroke, has become a leading cause of death in high-income countries and a major cause of morbidity around the world.5 Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.3,16 Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.6,7,8,9,10,14 Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.3,4 Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.11,12

While all statin medications are considered equally effective from a clinical standpoint, rosuvastatin is considered the most potent; doses of 10 to 40mg rosuvastatin per day were found in clinical studies to result in a 45.8% to 54.6% decrease in LDL cholesterol levels, while simvastatin has been found to have an average decrease in LDL-C of ~35%.13,14,18 Potency is thought to correlate to tissue permeability as the more lipophilic statins such as simvastatin are thought to enter endothelial cells by passive diffusion, as opposed to hydrophilic statins such as pravastatin and rosuvastatin which are taken up into hepatocytes through OATP1B1 (organic anion transporter protein 1B1)-mediated transport.15,20 Despite these differences in potency, several trials have demonstrated only minimal differences in terms of clinical outcomes between statins.9

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 418.5662
Monoisotopic: 418.271924326
Chemical Formula
C25H38O5
Synonyms
  • 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
  • Simvastatin
  • Simvastatina
  • Simvastatine
  • Simvastatinum
External IDs
  • MK 733
  • MK-0733
  • MK-733

Pharmacology

Indication

Simvastatin is indicated for the treatment of hyperlipidemia 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).28,29

This includes the treatment of primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial), mixed dyslipidemia (Fredrickson type IIb), hypertriglyceridemia (Fredrickson type IV hyperlipidemia), primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia), homozygous familial hypercholesterolemia (HoFH) as an adjunct to other lipid-lowering treatments, as well as adolescent patients with Heterozygous Familial Hypercholesterolemia (HeFH).28,29

Simvastatin is also indicated to reduce the risk of cardiovascular morbidity and mortality including myocardial infarction, stroke, and the need for revascularization procedures. It is primarily used 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.28,29

Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD. Statin-indicated conditions include diabetes mellitus, clinical atherosclerosis (including myocardial infarction, acute coronary syndromes, stable angina, documented coronary artery disease, stroke, trans ischemic attack (TIA), documented carotid disease, peripheral artery disease, and claudication), abdominal aortic aneurysm, chronic kidney disease, and severely elevated LDL-C levels.3,4

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Simvastatin is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.3,4

Elevated cholesterol levels, and in particular, elevated low-density lipoprotein (LDL) levels, are an important risk factor for the development of CVD.3 Use of statins to target and reduce LDL levels has been shown in a number of landmark studies to significantly reduce the risk of development of CVD and all-cause mortality.6,7,8,9,10 Statins are considered a cost-effective treatment option for CVD due to their evidence of reducing all-cause mortality including fatal and non-fatal CVD as well as the need for surgical revascularization or angioplasty following a heart attack.3,4 Evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within 5 years) statins cause a 20%-22% relative reduction in major cardiovascular events (heart attack, stroke, coronary revascularization, and coronary death) for every 1 mmol/L reduction in LDL without any significant side effects or risks.11,12

Skeletal Muscle Effects

Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. Chinese patients may also be at increased risk for myopathy. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued.28,29

In a clinical trial database of 41,413 patients, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively, while the risk of myopathy with simvastatin 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. It's therefore recommended that the 80mg dose of simvastatin should be used only in patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. As well, patients already stabilized on simvastatin 80mg should be monitored closely for evidence of muscle toxicity; if they need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin with less potential for the drug-drug interaction.28,29

The risk of myopathy during treatment with simvastatin may be increased with concurrent administration of interacting drugs such as fenofibrate, niacin, gemfibrozil, cyclosporine, and strong inhibitors of the CYP3A4 enzyme. Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with colchicine, and caution should therefore be exercised when prescribing these two medications together.28,29

Liver Enzyme Abnormalities

Persistent increases (to more than 3X the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. 28,29

In the Scandinavian Simvastatin Survival Study (4S),14 the number of patients with more than one transaminase elevation to >3 times the ULN, over the course of the study, was not significantly different between the simvastatin and placebo groups (14 [0.7%] vs. 12 [0.6%]). The frequency of single elevations of ALT to 3 times the ULN was significantly higher in the simvastatin group in the first year of the study (20 vs. 8, p=0.023), but not thereafter. In the HPS (Heart Protection Study),10 in which 20,536 patients were randomized to receive simvastatin 40 mg/day or placebo, the incidences of elevated transaminases (>3X ULN confirmed by repeat test) were 0.21% (n=21) for patients treated with simvastatin and 0.09% (n=9) for patients treated with placebo.28,29

Endocrine Effects

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.28

Although cholesterol is the precursor of all steroid hormones, studies with simvastatin have suggested that this agent has no clinical effect on steroidogenesis. Simvastatin caused no increase in biliary lithogenicity and, therefore, would not be expected to increase the incidence of gallstones.29

Mechanism of action

Simvastatin is a prodrug in which the 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis.2 Simvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Simvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL).28,29 The overall effect is a decrease in plasma LDL and VLDL.

At therapeutic doses, the HMG-CoA enzyme is not completely blocked by simvastatin activity, thereby allowing biologically necessary amounts of mevalonate to remain available. As mevalonate is an early step in the biosynthetic pathway for cholesterol, therapy with simvastatin would also not be expected to cause any accumulation of potentially toxic sterols. In addition, HMG-CoA is metabolized readily back to acetyl-CoA, which participates in many biosynthetic processes in the body.29

In vitro and in vivo animal studies also demonstrate that simvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins.15 This includes improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response.

Statins have also been found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an important role in leukocyte trafficking and in T cell activation.17

TargetActionsOrganism
A3-hydroxy-3-methylglutaryl-coenzyme A reductase
inhibitor
Humans
UIntegrin alpha-L
inhibitory allosteric modulator
Humans
UHistone deacetylase 2
inhibitor
Humans
Absorption

Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours post-dose. While the recommended therapeutic dose range is 10 to 40 mg/day, there was no substantial deviation from linearity of AUC with an increase in dose to as high as 120 mg. Relative to the fasting state, the plasma profile of inhibitors was not affected when simvastatin was administered immediately before a test meal.28,29

In a pharmacokinetic study of 17 healthy Chinese volunteers, the major PK parameters were as follows: Tmax 1.44 hours, Cmax 9.83 ug/L, t1/2 4.85 hours, and AUC 40.32ug·h/L.19

Simvastatin undergoes extensive first-pass extraction in the liver, the target organ for the inhibition of HMG-CoA reductase and the primary site of action. This tissue selectivity (and consequent low systemic exposure) of orally administered simvastatin has been shown to be far greater than that observed when the drug is administered as the enzymatically active form, i.e. as the open hydroxyacid.29

In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues. However, because simvastatin undergoes extensive first-pass metabolism, the bioavailability of the drug in the systemic system is low. In a single-dose study in nine healthy subjects, it was estimated that less than 5% of an oral dose of simvastatin reached the general circulation in the form of active inhibitors.29

Genetic differences in the OATP1B1 (Organic-Anion-Transporting Polypeptide 1B1) hepatic transporter encoded by the SCLCO1B1 gene (Solute Carrier Organic Anion Transporter family member 1B1) have been shown to impact simvastatin pharmacokinetics. Evidence from pharmacogenetic studies of the c.521T>C single nucleotide polymorphism (SNP) showed that simvastatin plasma concentrations were increased on average 3.2-fold for individuals homozygous for 521CC compared to homozygous 521TT individuals.22,21 The 521CC genotype is also associated with a marked increase in the risk of developing myopathy, likely secondary to increased systemic exposure.23 Other statin drugs impacted by this polymorphism include rosuvastatin, pitavastatin, atorvastatin, lovastatin, and pravastatin.20

For patients known to have the above-mentioned c.521CC OATP1B1 genotype, a maximum daily dose of 20mg of simvastatin is recommended to avoid adverse effects from the increased exposure to the drug, such as muscle pain and risk of rhabdomyolysis.29

Evidence has also been obtained with other statins such as rosuvastatin that concurrent use of statins and inhibitors of Breast Cancer Resistance Protein (BCRP) such as elbasvir and grazoprevir increased the plasma concentration of these statins. Further evidence is needed, however a dose adjustment of simvastatin may be necessary. Other statin drugs impacted by this polymorphism include fluvastatin and atorvastatin.21

Volume of distribution

Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin-derived radioactivity crossed the blood-brain barrier.28

Protein binding

Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins.28,29

Metabolism

Simvastatin is administered as the inactive lactone derivative that is then metabolically activated to its β-hydroxyacid form by a combination of spontaneous chemical conversion and enzyme-mediated hydrolysis by nonspecific carboxyesterases in the intestinal wall, liver, and plasma. Oxidative metabolism in the liver is primarily mediated by CYP3A4 and CYP3A5, with the remaining metabolism occurring through CYP2C8 and CYP2C9.25

The major active metabolites of simvastatin are β-hydroxyacid metabolite and its 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives.28,29

Polymorphisms in the CYP3A5 gene have been shown to affect the disposition of simvastatin and may provide a plausible explanation for interindividual variability of simvastatin disposition and pharmacokinetics.24

Hover over products below to view reaction partners

Route of elimination

Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.28,29

Half-life

4.85 hours19

Clearance
Not Available
Adverse Effects
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Simvastatin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Kinesin-like protein KIF6---(C;C) / (C;T)C AlleleEffect Directly StudiedPatients with this genotype have a greater reduction in risk of a major cardiovascular event with high dose simvastatin.Details
3-hydroxy-3-methylglutaryl-coenzyme A reductase---(A;T)T AlleleEffect Directly StudiedPatients with this genotype have a lesser reduction in LDL cholesterol with simvastatin.Details
Solute carrier organic anion transporter family member 1B1SLCO1B1*5(C;C) / (C;T)T > CADR Directly StudiedThe presence of this genotype in SLCO1B1 is associated with an increased risk of myopathy when treated with simvastatin.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Simvastatin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Simvastatin can be increased when combined with Abatacept.
AbirateroneThe metabolism of Simvastatin can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Simvastatin can be decreased when combined with Acalabrutinib.
AcebutololThe metabolism of Simvastatin can be decreased when combined with Acebutolol.
AcenocoumarolSimvastatin may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenThe metabolism of Simvastatin can be decreased when combined with Acetaminophen.
AcetohexamideThe metabolism of Acetohexamide can be decreased when combined with Simvastatin.
AcetylcysteineThe excretion of Simvastatin can be decreased when combined with Acetylcysteine.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Simvastatin.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products. Co-administration with grapefruit products may increase the risk for adverse effects such as myalgia.

Products

Product Images
International/Other Brands
Cholestat (Kalbe) / Colemin (Biohorm) / Labistatin (Sandoz) / Lipex (Merck Sharp & Dohme) / Medipo (Mediolanum Farmaceutici) / Nivelipol (Temis-Lostalo) / Simovil (Merck Sharp & Dohme) / Sinvacor (Merck Sharp & Dohme) / Sivastin (Sigma-Tau) / Sivatin (Rowex) / Sivinar (Anfarm) / Sorfox (Galex) / Sotovastin (Bros) / Starezin (Leovan Pharmaceuticals) / Starstat (Lupin) / Starzoko (Daewoong) / Stasiva (Pharmanel) / Statex (Pliva) / Staticor (Darnitsa) / Statinal (Alet Pharmaceuticals) / Stativer (Iapharm) / Synvinolin
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act SimvastatinTabletOralActavis Pharma Company2003-09-262018-06-11Canada flag
Act SimvastatinTabletOralActavis Pharma Company2003-09-262018-06-11Canada flag
Act SimvastatinTabletOralActavis Pharma Company2003-09-262018-06-11Canada flag
Act SimvastatinTabletOralActavis Pharma Company2003-09-262018-06-11Canada flag
Act SimvastatinTabletOralActavis Pharma Company2003-09-262018-06-11Canada flag
Bci SimvastatinTabletOralBaker Cummins IncNot applicableNot applicableCanada flag
Bci SimvastatinTabletOralBaker Cummins IncNot applicableNot applicableCanada flag
Bci SimvastatinTabletOralBaker Cummins IncNot applicableNot applicableCanada flag
Bci SimvastatinTabletOralBaker Cummins IncNot applicableNot applicableCanada flag
Bci SimvastatinTabletOralBaker Cummins IncNot applicableNot applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ag-simvastatinTabletOralAngita Pharma Inc.2018-09-06Not applicableCanada flag
Ag-simvastatinTabletOralAngita Pharma Inc.2018-09-06Not applicableCanada flag
Ag-simvastatinTabletOralAngita Pharma Inc.2018-09-06Not applicableCanada flag
Ag-simvastatinTabletOralAngita Pharma Inc.2018-09-06Not applicableCanada flag
Ag-simvastatinTabletOralAngita Pharma Inc.2018-09-06Not applicableCanada flag
Apo-simvastatinTabletOralApotex Corporation2002-12-20Not applicableCanada flag
Apo-simvastatinTabletOralApotex Corporation2002-12-20Not applicableCanada flag
Apo-simvastatinTabletOralApotex Corporation2002-12-20Not applicableCanada flag
Apo-simvastatinTabletOralApotex Corporation2002-12-20Not applicableCanada flag
Apo-simvastatinTabletOralApotex Corporation2002-12-20Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
CholibSimvastatin (20 mg) + Fenofibrate (145 mg)Tablet, film coatedOralMylan Products Limited2013-08-26Not applicableEU flag
CholibSimvastatin (40 mg) + Fenofibrate (145 mg)Tablet, film coatedOralMylan Products Limited2013-08-26Not applicableEU flag
CholibSimvastatin (20 mg) + Fenofibrate (145 mg)Tablet, film coatedOralMylan Products Limited2013-08-26Not applicableEU flag
CholibSimvastatin (40 mg) + Fenofibrate (145 mg)Tablet, film coatedOralMylan Products Limited2013-08-26Not applicableEU flag
CholibSimvastatin (40 mg) + Fenofibrate (145 mg)Tablet, film coatedOralMylan Products Limited2013-08-26Not applicableEU flag
CholibSimvastatin (20 mg) + Fenofibrate (145 mg)Tablet, film coatedOralMylan Products Limited2013-08-26Not applicableEU flag
Ezetimibe and SimvastatinSimvastatin (10 mg/1) + Ezetimibe (10 mg/1)Tablet, film coatedOralImpax Generics2017-04-262020-05-31US flag
Ezetimibe and SimvastatinSimvastatin (10 mg/1) + Ezetimibe (10 mg/1)TabletOralAscend Laboratories, LLC2017-12-24Not applicableUS flag
Ezetimibe and SimvastatinSimvastatin (80 mg/1) + Ezetimibe (10 mg/1)TabletOralGlenmark Pharmaceuticals Inc., USA2019-06-27Not applicableUS flag
Ezetimibe and SimvastatinSimvastatin (20 mg/1) + Ezetimibe (10 mg/1)TabletOralDr.Reddys Laboratories Inc2017-04-26Not applicableUS flag

Categories

ATC Codes
A10BH51 — Sitagliptin and simvastatinC10AA01 — SimvastatinC10BX04 — Simvastatin, acetylsalicylic acid and ramiprilC10BA02 — Simvastatin and ezetimibeC10BX01 — Simvastatin and acetylsalicylic acidC10BA04 — Simvastatin and fenofibrate
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as delta valerolactones. These are cyclic organic compounds containing an oxan-2- one moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactones
Sub Class
Delta valerolactones
Direct Parent
Delta valerolactones
Alternative Parents
Fatty acid esters / Oxanes / Dicarboxylic acids and derivatives / Secondary alcohols / Carboxylic acid esters / Oxacyclic compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Alcohol / Aliphatic heteropolycyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Delta valerolactone / Delta_valerolactone / Dicarboxylic acid or derivatives / Fatty acid ester / Fatty acyl
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
statin (semi-synthetic), fatty acid ester, delta-lactone, carbobicyclic compound (CHEBI:9150)

Chemical Identifiers

UNII
AGG2FN16EV
CAS number
79902-63-9
InChI Key
RYMZZMVNJRMUDD-HGQWONQESA-N
InChI
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
IUPAC Name
(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate
SMILES

References

Synthesis Reference

Shieh-Shung J. Chen, Byron H. Arison, "Process for the preparation of 3-keto, 5-hydroxy simvastatin analogs." U.S. Patent US4965200, issued April, 1981.

US4965200
General References
  1. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE: Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med. 2007 Jul 19;5:20. [PubMed:17640385]
  2. Moghadasian MH: Clinical pharmacology of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Life Sci. 1999;65(13):1329-37. doi: 10.1016/s0024-3205(99)00199-x. [PubMed:10503952]
  3. Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, Francis GA, Genest J Jr, Grover S, Gupta M, Hegele RA, Lau DC, Leiter LA, Lonn E, Mancini GB, McPherson R, Ngui D, Poirier P, Sievenpiper JL, Stone JA, Thanassoulis G, Ward R: 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25. [PubMed:27712954]
  4. Grundy SM, Stone NJ: 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol: Primary Prevention. JAMA Cardiol. 2019 Apr 10. pii: 2730287. doi: 10.1001/jamacardio.2019.0777. [PubMed:30969322]
  5. Kreatsoulas C, Anand SS: The impact of social determinants on cardiovascular disease. Can J Cardiol. 2010 Aug-Sep;26 Suppl C:8C-13C. doi: 10.1016/s0828-282x(10)71075-8. [PubMed:20847985]
  6. Authors unspecified: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339(19):1349-57. doi: 10.1056/NEJM199811053391902. [PubMed:9841303]
  7. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8. [PubMed:15007110]
  8. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ: Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. doi: 10.1056/NEJMoa0807646. Epub 2008 Nov 9. [PubMed:18997196]
  9. Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE: Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011 Dec 1;365(22):2078-87. doi: 10.1056/NEJMoa1110874. Epub 2011 Nov 15. [PubMed:22085316]
  10. Authors unspecified: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 Jul 6;360(9326):7-22. doi: 10.1016/S0140-6736(02)09327-3. [PubMed:12114036]
  11. Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C: The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012 Aug 11;380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17. [PubMed:22607822]
  12. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, Ward K, Ebrahim S: Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD004816. doi: 10.1002/14651858.CD004816.pub5. [PubMed:23440795]
  13. Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, Larsen ML, Bendiksen FS, Lindahl C, Szarek M, Tsai J: High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005 Nov 16;294(19):2437-45. doi: 10.1001/jama.294.19.2437. [PubMed:16287954]
  14. Authors unspecified: Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) Lancet. 1994 Nov 19;344(8934):1383-9. [PubMed:7968073]
  15. Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi: 10.1146/annurev.pharmtox.45.120403.095748. [PubMed:15822172]
  16. Kannel WB, Castelli WP, Gordon T, McNamara PM: Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med. 1971 Jan;74(1):1-12. doi: 10.7326/0003-4819-74-1-1. [PubMed:5539274]
  17. Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U: Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med. 2001 Jun;7(6):687-92. doi: 10.1038/89058. [PubMed:11385505]
  18. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW: Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60. [PubMed:12860216]
  19. Zhou Q, Ruan ZR, Jiang B, Yuan H, Zeng S: Simvastatin pharmacokinetics in healthy Chinese subjects and its relations with CYP2C9, CYP3A5, ABCB1, ABCG2 and SLCO1B1 polymorphisms. Pharmazie. 2013 Feb;68(2):124-8. [PubMed:23469684]
  20. Elsby R, Hilgendorf C, Fenner K: Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1. Clin Pharmacol Ther. 2012 Nov;92(5):584-98. doi: 10.1038/clpt.2012.163. Epub 2012 Oct 10. [PubMed:23047648]
  21. Keskitalo JE, Zolk O, Fromm MF, Kurkinen KJ, Neuvonen PJ, Niemi M: ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther. 2009 Aug;86(2):197-203. doi: 10.1038/clpt.2009.79. Epub 2009 May 27. [PubMed:19474787]
  22. Pasanen MK, Neuvonen M, Neuvonen PJ, Niemi M: SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet Genomics. 2006 Dec;16(12):873-9. doi: 10.1097/01.fpc.0000230416.82349.90. [PubMed:17108811]
  23. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, Gut I, Lathrop M, Collins R: SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789-99. doi: 10.1056/NEJMoa0801936. Epub 2008 Jul 23. [PubMed:18650507]
  24. Kim KA, Park PW, Lee OJ, Kang DK, Park JY: Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J Clin Pharmacol. 2007 Jan;47(1):87-93. doi: 10.1177/0091270006295063. [PubMed:17192506]
  25. Tubic-Grozdanis M, Hilfinger JM, Amidon GL, Kim JS, Kijek P, Staubach P, Langguth P: Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Pharm Res. 2008 Jul;25(7):1591-600. doi: 10.1007/s11095-007-9519-6. Epub 2008 Jan 24. [PubMed:18213452]
  26. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
  27. ZOCOR FDA Label [Link]
  28. FDA Label - Simvastatin [File]
  29. Health Canada Monograph - Simvastatin [File]
Human Metabolome Database
HMDB0005007
KEGG Drug
D00434
PubChem Compound
54454
PubChem Substance
46508654
ChemSpider
49179
BindingDB
50139181
RxNav
36567
ChEBI
9150
ChEMBL
CHEMBL1064
ZINC
ZINC000003780893
Therapeutic Targets Database
DAP001519
PharmGKB
PA451363
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Simvastatin
AHFS Codes
  • 24:06.08 — Hmg-coa Reductase Inhibitors
MSDS
Download (87.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingDiagnosticSkeletal Myopathy / Statin Adverse Reaction1
4Active Not RecruitingPreventionMild Cognitive Impairment (MCI)1
4Active Not RecruitingTreatmentBipolar Disorder (BD) / Cardiovascular Heart Disease / Major Depressive Disorder (MDD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenia / Serious Mental Illness1
4CompletedNot AvailableCardiovascular Heart Disease / Cholesterol, LDL / Cognition / Type 2 Diabetes Mellitus1
4CompletedNot AvailableCoronary Heart Disease (CHD)1
4CompletedNot AvailableDyslipidemia1
4CompletedBasic ScienceAtherosclerosis1
4CompletedBasic ScienceCardiovascular Heart Disease / Diabetes Mellitus1
4CompletedDiagnosticHealthy Men1
4CompletedHealth Services ResearchDiabetes Mellitus / Dyslipidemia1

Pharmacoeconomics

Manufacturers
  • Synthon pharmaceuticals ltd
  • Accord healthcare inc
  • Aurobindo pharma ltd
  • Dr reddys laboratories inc
  • Dr reddys laboratories ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lupin ltd
  • Matrix laboratories ltd
  • Perrigo r and d co
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
  • Merck research laboratories div merck co inc
Packagers
  • Abbott Laboratories Ltd.
  • Accord Healthcare
  • Advanced Pharmaceutical Services Inc.
  • Aeropharm Technology LLC
  • Amerisource Health Services Corp.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Aurobindo Pharma Ltd.
  • Blenheim Pharmacal
  • Blu Pharmaceuticals LLC
  • Bryant Ranch Prepack
  • Cadila Healthcare Ltd.
  • Cardinal Health
  • Cobalt Pharmaceuticals Inc.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • Intas Pharmaceuticals Ltd.
  • Kaiser Foundation Hospital
  • Laboratorios Belmac SA
  • Lake Erie Medical and Surgical Supply
  • Lupin Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • Medisca Inc.
  • Medvantx Inc.
  • Merck & Co.
  • MSP Distribution Services LLC
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Northstar Rx LLC
  • Nucare Pharmaceuticals Inc.
  • Ohm Laboratories Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Stat Scripts LLC
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
Tablet, film coatedOral
Tablet, film coatedOral145 MG
Capsule, liquid filledOral10 mg
Tablet, coatedOral10 mg
TabletOral80 MG
TabletOral10 mg
SuspensionOral20 mg/5mL
SuspensionOral40 mg/5mL
Tablet, film coated10 mg
Tablet, film coated20 mg
Tablet, film coated40 mg
Tablet, film coated80 mg
TabletOral
Tablet, film coated, extended releaseOral
Tablet, film coatedOral10 MG
Tablet, film coatedOral20 MG
Tablet, film coatedOral30 MG
Tablet, film coatedOral40 MG
Tablet, film coatedOral60 MG
Tablet, film coatedOral80 MG
Tablet, film coatedOral5 MG
Tablet80 mg
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral40 mg/1
TabletOral5 mg
TabletOral5 mg/1
TabletOral80 mg/1
Tablet, coatedOral10 mg/1
Tablet, coatedOral20 mg/1
Tablet, coatedOral40 mg/1
Tablet, coatedOral5 mg/1
Tablet, coatedOral80 mg/1
Tablet, film coatedOral
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral40 mg/1
Tablet, film coatedOral5 mg/1
Tablet, film coatedOral80 mg/1
Tablet, film coatedPeriarticular80 mg/1
Tablet, orally disintegratingOral10 mg/1
Tablet, orally disintegratingOral20 mg/1
Tablet, orally disintegratingOral40 mg/1
Tablet, orally disintegratingOral80 mg/1
Tablet, coatedOral20 mg
TabletOral20 mg
TabletOral40 mg
Tablet, coatedOral40 mg
Tablet, coatedOral5 MG
Tablet, coatedOral80 MG
Tablet10 mg
TabletOral
Tablet
Prices
Unit descriptionCostUnit
Zocor 90 40 mg tablet Bottle525.16USD bottle
Simvastatin 100% powder10.71USD g
Vytorin 10-20 mg tablet5.05USD tablet
Vytorin 10-40 mg tablet5.05USD tablet
Vytorin 10-10 mg tablet4.97USD tablet
Zocor 20 mg tablet4.69USD tablet
Zocor 80 mg tablet4.69USD tablet
Vytorin 10-80 mg tablet4.63USD tablet
Zocor 40 mg tablet4.11USD tablet
Simvastatin 20 mg tablet3.83USD tablet
Simvastatin 40 mg tablet3.83USD tablet
Simvastatin 80 mg tablet3.83USD tablet
Zocor 10 mg tablet2.89USD tablet
Simvastatin 10 mg tablet2.31USD tablet
Zocor 5 mg tablet1.99USD tablet
Simvastatin 5 mg tablet1.63USD tablet
Phl-Simvastatin 40 mg Tablet1.45USD tablet
Phl-Simvastatin 80 mg Tablet1.45USD tablet
Pms-Simvastatin 20 mg Tablet1.45USD tablet
Pms-Simvastatin 40 mg Tablet1.45USD tablet
Pms-Simvastatin 80 mg Tablet1.45USD tablet
Ran-Simvastatin 20 mg Tablet1.45USD tablet
Ran-Simvastatin 40 mg Tablet1.45USD tablet
Ran-Simvastatin 80 mg Tablet1.45USD tablet
Ratio-Simvastatin 20 mg Tablet1.45USD tablet
Ratio-Simvastatin 40 mg Tablet1.45USD tablet
Ratio-Simvastatin 80 mg Tablet1.45USD tablet
Sandoz Simvastatin 20 mg Tablet1.45USD tablet
Sandoz Simvastatin 40 mg Tablet1.45USD tablet
Sandoz Simvastatin 80 mg Tablet1.45USD tablet
Apo-Simvastatin 20 mg Tablet1.45USD tablet
Apo-Simvastatin 40 mg Tablet1.45USD tablet
Apo-Simvastatin 80 mg Tablet1.45USD tablet
Co Simvastatin 20 mg Tablet1.45USD tablet
Co Simvastatin 40 mg Tablet1.45USD tablet
Co Simvastatin 80 mg Tablet1.45USD tablet
Jamp-Simvastatin 20 mg Tablet1.45USD tablet
Jamp-Simvastatin 40 mg Tablet1.45USD tablet
Jamp-Simvastatin 80 mg Tablet1.45USD tablet
Mylan-Simvastatin 20 mg Tablet1.45USD tablet
Mylan-Simvastatin 40 mg Tablet1.45USD tablet
Mylan-Simvastatin 80 mg Tablet1.45USD tablet
Novo-Simvastatin 20 mg Tablet1.45USD tablet
Novo-Simvastatin 40 mg Tablet1.45USD tablet
Novo-Simvastatin 80 mg Tablet1.45USD tablet
Phl-Simvastatin 20 mg Tablet1.45USD tablet
Apo-Simvastatin 10 mg Tablet1.17USD tablet
Co Simvastatin 10 mg Tablet1.17USD tablet
Jamp-Simvastatin 10 mg Tablet1.17USD tablet
Mylan-Simvastatin 10 mg Tablet1.17USD tablet
Novo-Simvastatin 10 mg Tablet1.17USD tablet
Phl-Simvastatin 10 mg Tablet1.17USD tablet
Pms-Simvastatin 10 mg Tablet1.17USD tablet
Ran-Simvastatin 10 mg Tablet1.17USD tablet
Ratio-Simvastatin 10 mg Tablet1.17USD tablet
Sandoz Simvastatin 10 mg Tablet1.17USD tablet
Apo-Simvastatin 5 mg Tablet0.59USD tablet
Co Simvastatin 5 mg Tablet0.59USD tablet
Jamp-Simvastatin 5 mg Tablet0.59USD tablet
Mylan-Simvastatin 5 mg Tablet0.59USD tablet
Novo-Simvastatin 5 mg Tablet0.59USD tablet
Phl-Simvastatin 5 mg Tablet0.59USD tablet
Pms-Simvastatin 5 mg Tablet0.59USD tablet
Ran-Simvastatin 5 mg Tablet0.59USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5846966No1998-12-082013-09-21US flag
US7326708No2008-02-052026-04-11US flag
US6080428No2000-06-272017-05-27US flag
US6469035No2002-10-222018-03-15US flag
US6699871No2004-03-022022-07-26US flag
US7125873No2006-10-242022-07-26US flag
USRE37721Yes2002-05-282017-04-25US flag
USRE42461Yes2011-06-142017-04-25US flag
US6303661No2001-10-162017-04-24US flag
US6890898No2005-05-102019-02-02US flag
US7078381No2006-07-182019-02-02US flag
US7459428No2008-12-022019-02-02US flag
US8168637No2012-05-012022-06-26US flag
US9597289No2017-03-212030-02-23US flag
US10300041No2019-05-282027-04-26US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)135-138 °CPhysProp
water solubilityInsoluble FDA label
logP4.68HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0122 mg/mLALOGPS
logP4.51ALOGPS
logP4.46ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)14.91ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.83 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity117.68 m3·mol-1ChemAxon
Polarizability47.88 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9475
Blood Brain Barrier+0.9422
Caco-2 permeable-0.5951
P-glycoprotein substrateSubstrate0.8508
P-glycoprotein inhibitor IInhibitor0.7335
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterNon-inhibitor0.8435
CYP450 2C9 substrateNon-substrate0.835
CYP450 2D6 substrateNon-substrate0.9254
CYP450 3A4 substrateSubstrate0.7513
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9307
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.792
CarcinogenicityNon-carcinogens0.9408
BiodegradationNot ready biodegradable0.9657
Rat acute toxicity2.0061 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8921
hERG inhibition (predictor II)Non-inhibitor0.8573
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-3900000000-d04758924bf88a90c017
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0fya-0988400000-d9778b2f11696b81fb07
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-006w-0790000000-4f23e0376d85845e0964
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05i1-0940000000-058f6298af54c05532ed
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0092-0910000000-6ecd838b2f6fddf67dad
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0597-0900000000-012d0d6fcabbd21d696d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000e-0590000000-7f99e0b9531d4f42831a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0092-1960000000-e8429bbec985c5ecdd2d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0592-1910000000-dc09a51ca37fe4d24a5a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0abd-1900000000-9b55821f49270e5dd598
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0536-1900000000-d8a41a97ccbdb30e5a5e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-002f-2900000000-abe04d7f99c3eb0f2fcb

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nadph binding
Specific Function
Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including...
Gene Name
HMGCR
Uniprot ID
P04035
Uniprot Name
3-hydroxy-3-methylglutaryl-coenzyme A reductase
Molecular Weight
97475.155 Da
References
  1. Cenedella RJ, Kuszak JR, Al-Ghoul KJ, Qin S, Sexton PS: Discordant expression of the sterol pathway in lens underlies simvastatin-induced cataracts in Chbb: Thom rats. J Lipid Res. 2003 Jan;44(1):198-211. [PubMed:12518039]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Kocarek TA, Dahn MS, Cai H, Strom SC, Mercer-Haines NA: Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes. Drug Metab Dispos. 2002 Dec;30(12):1400-5. [PubMed:12433810]
  4. Liu L, Zhang R, Zhao JJ, Rogers JD, Hsieh JY, Fang W, Matuszewski BK, Dobrinska MR: Determination of simvastatin-derived HMG-CoA reductase inhibitors in biomatrices using an automated enzyme inhibition assay with radioactivity detection. J Pharm Biomed Anal. 2003 Apr 24;32(1):107-23. [PubMed:12852453]
  5. Pappu AS, Bacon SP, Illingworth DR: Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. J Lab Clin Med. 2003 Apr;141(4):250-6. [PubMed:12677170]
  6. Stoebner PE, Michot C, Ligeron C, Durand L, Meynadier J, Meunier L: [Simvastatin-induced lichen planus pemphigoides]. Ann Dermatol Venereol. 2003 Feb;130(2 Pt 1):187-90. [PubMed:12671581]
  7. Carbonell T, Freire E: Binding thermodynamics of statins to HMG-CoA reductase. Biochemistry. 2005 Sep 6;44(35):11741-8. [PubMed:16128575]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitory allosteric modulator
General Function
Metal ion binding
Specific Function
Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated ...
Gene Name
ITGAL
Uniprot ID
P20701
Uniprot Name
Integrin alpha-L
Molecular Weight
128768.495 Da
References
  1. Katano H, Pesnicak L, Cohen JI: Simvastatin induces apoptosis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and delays development of EBV lymphomas. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4960-5. Epub 2004 Mar 23. [PubMed:15041742]
  2. Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U: Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med. 2001 Jun;7(6):687-92. doi: 10.1038/89058. [PubMed:11385505]
  3. Liao JK, Laufs U: Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89-118. doi: 10.1146/annurev.pharmtox.45.120403.095748. [PubMed:15822172]
  4. Fujii T, Masuyama K, Kawashima K: Simvastatin regulates non-neuronal cholinergic activity in T lymphocytes via CD11a-mediated pathways. J Neuroimmunol. 2006 Oct;179(1-2):101-7. Epub 2006 Jul 10. [PubMed:16828882]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcription factor binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC2
Uniprot ID
Q92769
Uniprot Name
Histone deacetylase 2
Molecular Weight
55363.855 Da
References
  1. Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC: Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res. 2008 Apr 1;68(7):2375-83. doi: 10.1158/0008-5472.CAN-07-5807. [PubMed:18381445]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Neuvonen PJ, Niemi M, Backman JT: Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81. doi: 10.1016/j.clpt.2006.09.003. [PubMed:17178259]
  2. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. [PubMed:11523064]
  3. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  4. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [PubMed:12433827]
  5. Elsby R, Hilgendorf C, Fenner K: Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1. Clin Pharmacol Ther. 2012 Nov;92(5):584-98. doi: 10.1038/clpt.2012.163. Epub 2012 Oct 10. [PubMed:23047648]
  6. Kim KA, Park PW, Lee OJ, Kang DK, Park JY: Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J Clin Pharmacol. 2007 Jan;47(1):87-93. doi: 10.1177/0091270006295063. [PubMed:17192506]
  7. Tubic-Grozdanis M, Hilfinger JM, Amidon GL, Kim JS, Kijek P, Staubach P, Langguth P: Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Pharm Res. 2008 Jul;25(7):1591-600. doi: 10.1007/s11095-007-9519-6. Epub 2008 Jan 24. [PubMed:18213452]
  8. Flockhart Table of Drug Interactions [Link]
  9. Website [Link]
  10. FDA Label - Simvastatin [File]
  11. Health Canada Monograph - Simvastatin [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Kim KA, Park PW, Lee OJ, Kang DK, Park JY: Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J Clin Pharmacol. 2007 Jan;47(1):87-93. doi: 10.1177/0091270006295063. [PubMed:17192506]
  2. Tubic-Grozdanis M, Hilfinger JM, Amidon GL, Kim JS, Kijek P, Staubach P, Langguth P: Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Pharm Res. 2008 Jul;25(7):1591-600. doi: 10.1007/s11095-007-9519-6. Epub 2008 Jan 24. [PubMed:18213452]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Neuvonen PJ, Niemi M, Backman JT: Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81. doi: 10.1016/j.clpt.2006.09.003. [PubMed:17178259]
  2. Tornio A, Pasanen MK, Laitila J, Neuvonen PJ, Backman JT: Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8. Basic Clin Pharmacol Toxicol. 2005 Aug;97(2):104-8. [PubMed:15998357]
  3. Daily EB, Aquilante CL: Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies. Pharmacogenomics. 2009 Sep;10(9):1489-510. doi: 10.2217/pgs.09.82. [PubMed:19761371]
  4. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Supporting data are limited to findings of in vitro studies.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. [PubMed:11523064]
  2. Transon C, Leemann T, Dayer P: In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996;50(3):209-15. [PubMed:8737761]
  3. Tubic-Grozdanis M, Hilfinger JM, Amidon GL, Kim JS, Kijek P, Staubach P, Langguth P: Pharmacokinetics of the CYP 3A substrate simvastatin following administration of delayed versus immediate release oral dosage forms. Pharm Res. 2008 Jul;25(7):1591-600. doi: 10.1007/s11095-007-9519-6. Epub 2008 Jan 24. [PubMed:18213452]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Vermes A, Vermes I: Genetic polymorphisms in cytochrome P450 enzymes: effect on efficacy and tolerability of HMG-CoA reductase inhibitors. Am J Cardiovasc Drugs. 2004;4(4):247-55. [PubMed:15285699]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742]
  3. Kocarek TA, Dahn MS, Cai H, Strom SC, Mercer-Haines NA: Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes. Drug Metab Dispos. 2002 Dec;30(12):1400-5. [PubMed:12433810]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Wang E, Casciano CN, Clement RP, Johnson WW: HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm Res. 2001 Jun;18(6):800-6. [PubMed:11474784]
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514]
  3. Hochman JH, Pudvah N, Qiu J, Yamazaki M, Tang C, Lin JH, Prueksaritanont T: Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharm Res. 2004 Sep;21(9):1686-91. [PubMed:15497697]
  4. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M: Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int J Cancer. 2010 May 1;126(9):2025-35. doi: 10.1002/ijc.24885. [PubMed:19739078]
  5. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. [PubMed:10601278]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. [PubMed:10601278]
  2. Kameyama Y, Yamashita K, Kobayashi K, Hosokawa M, Chiba K: Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenet Genomics. 2005 Jul;15(7):513-22. [PubMed:15970799]
  3. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
  4. Elsby R, Hilgendorf C, Fenner K: Understanding the critical disposition pathways of statins to assess drug-drug interaction risk during drug development: it's not just about OATP1B1. Clin Pharmacol Ther. 2012 Nov;92(5):584-98. doi: 10.1038/clpt.2012.163. Epub 2012 Oct 10. [PubMed:23047648]
  5. Pasanen MK, Neuvonen M, Neuvonen PJ, Niemi M: SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet Genomics. 2006 Dec;16(12):873-9. doi: 10.1097/01.fpc.0000230416.82349.90. [PubMed:17108811]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Becker ML, Elens LL, Visser LE, Hofman A, Uitterlinden AG, van Schaik RH, Stricker BH: Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy. Pharmacogenomics J. 2013 Jun;13(3):251-6. doi: 10.1038/tpj.2011.59. Epub 2011 Dec 20. [PubMed:22186618]
  2. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Kitzmiller JP, Mikulik EB, Dauki AM, Murkherjee C, Luzum JA: Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106. doi: 10.2147/PGPM.S86013. eCollection 2016. [PubMed:27757045]

Drug created on June 13, 2005 07:24 / Updated on October 21, 2020 01:55

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