Identification

Name
Atorvastatin
Accession Number
DB01076
Description

Atorvastatin (Lipitor®), is a lipid-lowering drug included in the statin class of medications. By inhibiting the endogenous production of cholesterol in the liver, statins lower abnormal cholesterol and lipid levels, and ultimately reduce the risk of cardiovascular disease. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase,8 which catalyzes the conversion of HMG-CoA to mevalonic acid. This conversion is a critical metabolic reaction 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 statins is considered standard practice for patients following any cardiovascular event, and for people who are at moderate to high risk of developing cardiovascular disease. The evidence supporting statin use, coupled with minimal side effects and long term benefits, has resulted in wide use of this medication in North America.9,10

Atorvastatin and other statins including lovastatin, pravastatin, rosuvastatin, fluvastatin, and simvastatin are considered first-line treatment options for dyslipidemia.9,10 The increasing use of this class of drugs is largely attributed to the rise in cardiovascular diseases (CVD) (such as heart attack, atherosclerosis, angina, peripheral artery disease, and stroke) in many countries.11 An elevated cholesterol level (elevated low-density lipoprotein (LDL) levels in particular) is a significant risk factor for the development of CVD.9,12 Several landmark studies demonstrate that the use of statins is associated with both a reduction in LDL levels and CVD risk.13,14,15,16,17,18 Statins were shown to reduce the incidences of all-cause mortality, including fatal and non-fatal CVD, as well as the need for surgical revascularization or angioplasty following a heart attack.9,10 Some evidence has shown that even for low-risk individuals (with <10% risk of a major vascular event occurring within five years) statin use leads to a 20%-22% relative reduction in the number of 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.19,20

Atorvastatin was first synthesized in 1985 by Dr. Bruce Roth and approved by the FDA in 1996.33 It is a pentasubstituted pyrrole 3 formed by two contrasting moieties with an achiral heterocyclic core unit and a 3,5-dihydroxypentanoyl side chain identical to its parent compound.34 Unlike other members of the statin group, atorvastatin is an active compound and therefore does not require activation.4

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 558.6398
Monoisotopic: 558.253000445
Chemical Formula
C33H35FN2O5
Synonyms
  • Atorvastatin
  • atorvastatina
  • atorvastatine
  • atorvastatinum

Pharmacology

Indication

Atorvastatin is indicated for the treatment of several types of dyslipidemias, including primary hyperlipidemia and mixed dyslipidemia in adults, hypertriglyceridemia, primary dysbetalipoproteinemia, homozygous familial hypercholesterolemia, and heterozygous familial hypercholesterolemia in adolescent patients with failed dietary modifications.2

Dyslipidemia describes an elevation of plasma cholesterol, triglycerides or both as well as to the presence of low levels of high-density lipoprotein. This condition represents an increased risk for the development of atherosclerosis.35

Atorvastatin is indicated, in combination with dietary modifications, to prevent cardiovascular events in patients with cardiac risk factors and/or abnormal lipid profiles.2

Atorvastatin can be used as a preventive agent for myocardial infarction, stroke, revascularization, and angina, in patients without coronary heart disease but with multiple risk factors and in patients with type 2 diabetes without coronary heart disease but multiple risk factors.2

Atorvastatin may be used as a preventive agent for non-fatal myocardial infarction, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure and angina in patients with coronary heart disease.2

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.9,10

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Atorvastatin is an oral antilipemic agent that reversibly inhibits HMG-CoA reductase. It lowers total cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apo B), non-high density lipoprotein-cholesterol (non-HDL-C), and triglyceride (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 a 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, atorvastatin reduces the risk of cardiovascular morbidity and mortality.21,9,10,27

Elevated cholesterol levels (and high low-density lipoprotein (LDL) levels in particular) are an important risk factor for the development of CVD.9 Clinical studies have shown that atorvastatin reduces LDL-C and total cholesterol by 36-53%.3 In patients with dysbetalipoproteinemia, atorvastatin reduced the levels of intermediate-density lipoprotein cholesterol.2 It has also been suggested that atorvastatin can limit the extent of angiogenesis, which can be useful in the treatment of chronic subdural hematoma.1

Myopathy/Rhabdomyolysis

Atorvastatin, like other HMG-CoA reductase inhibitors, is associated with a risk of drug-induced myopathy characterized by muscle pain, tenderness, or weakness in conjunction with elevated levels of creatine kinase (CK). Myopathy often manifests as rhabdomyolysis with or without acute renal failure secondary to myoglobinuria. The risk of statin-induced myopathy is dose-related, and the symptoms of myopathy are typically resolved upon drug discontinuation. Results from observational studies suggest that 10-15% of people taking statins may experience muscle aches at some point during treatment.30

Liver Dysfunction

Statins, like some other lipid-lowering therapies, have been associated with biochemical abnormalities of liver function. Persistent elevations (> 3 times the upper limit of normal [ULN] occurring on two or more occasions) in serum transaminases occurred in 0.7% of patients who received atorvastatin in clinical trials. This effect appears to be dose-related.39,40

Endocrine Effects

Statins are associated with a risk of increased serum HbA1c and glucose levels. An in vitro study demonstrated a dose-dependent cytotoxic effect on human pancreatic islet β cells following treatment with atorvastatin. Moreover, insulin secretion rates decreased relative to control.7

HMG-CoA reductase inhibitors interfere with cholesterol synthesis and may theoretically interfere with the production of adrenal and/or gonadal steroids. Clinical studies with atorvastatin and other HMG-CoA reductase inhibitors have suggested that these agents do not affect plasma cortisol concentrations, basal plasma testosterone concentration, or adrenal reserve. However, the effect of statins on male fertility has not been fully investigated. The effects of statins on the pituitary-gonadal axis in premenopausal women are unknown.40

Cardiovascular

Significant decreases in circulating ubiquinone levels in patients treated with atorvastatin and other statins have been observed. The clinical significance of a potential long-term statin-induced deficiency of ubiquinone has not been established. It has been reported that a decrease in myocardial ubiquinone levels could lead to impaired cardiac function in patients with borderline congestive heart failure.40

Lipoprotein A

In some patients, the beneficial effect of lowered total cholesterol and LDL-C levels may be partly blunted by the concomitant increase in Lp(a) lipoprotein concentrations. Present knowledge suggests the importance of high Lp(a) levels as an emerging risk factor for coronary heart disease.40 Further studies have demonstrated statins affect Lp(a) levels differently in patients with dyslipidemia depending on their apo(a) phenotype; statins increase Lp(a) levels exclusively in patients with the low molecular weight apo(a) phenotype.28

Mechanism of action

Atorvastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis.1,8 Atorvastatin 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. Atorvastatin also reduces Very-Low-Density Lipoprotein-Cholesterol (VLDL-C), serum triglycerides (TG) and Intermediate Density Lipoproteins (IDL), as well as the number of apolipoprotein B (apo B) containing particles, but increases High-Density Lipoprotein Cholesterol (HDL-C).

In vitro and in vivo animal studies also demonstrate that atorvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins.25 These effects include improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response. Statins were also found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an essential role in leukocyte trafficking and T cell activation.29

TargetActionsOrganism
A3-hydroxy-3-methylglutaryl-coenzyme A reductase
inhibitor
Humans
UDipeptidyl peptidase 4
inhibitor
Humans
UAryl hydrocarbon receptor
agonist
Humans
UHistone deacetylase 2
inhibitor
Humans
UNuclear receptor subfamily 1 group I member 3
ligand
Humans
Absorption

Atorvastatin presents a dose-dependent and non-linear pharmacokinetic profile.4 It is very rapidly absorbed after oral administration. After the administration of a dose of 40 mg, its peak plasma concentration of 28 ng/ml is reached 1-2 hours after initial administration with an AUC of about 200 ng∙h/ml.6 Atorvastatin undergoes extensive first-pass metabolism in the wall of the gut and the liver, resulting in an absolute oral bioavailability of 14%.2 Plasma atorvastatin concentrations are lower (approximately 30% for Cmax and AUC) following evening drug administration compared with morning. However, LDL-C reduction is the same regardless of the time of day of drug administration.39

Administration of atorvastatin with food results in prolonged Tmax and a reduction in Cmax and AUC.3

Breast Cancer Resistance Protein (BCRP) is a membrane-bound protein that plays an important role in the absorption of atorvastatin.26 Evidence from pharmacogenetic studies of c.421C>A single nucleotide polymorphisms (SNPs) in the gene for BCRP has demonstrated that individuals with the 421AA genotype have reduced functional activity and 1.72-fold higher AUC for atorvastatin compared to study individuals with the control 421CC genotype. This has important implications for the variation in response to the drug in terms of efficacy and toxicity, particularly as the BCRP c.421C>A polymorphism occurs more frequently in Asian populations than in Caucasians.31,32 Other statin drugs impacted by this polymorphism include fluvastatin, simvastatin, and rosuvastatin.31

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 atorvastatin pharmacokinetics. Evidence from pharmacogenetic studies of the c.521T>C single nucleotide polymorphism (SNP) in the gene encoding OATP1B1 (SLCO1B1) demonstrated that atorvastatin AUC was increased 2.45-fold for individuals homozygous for 521CC compared to homozygous 521TT individuals.[A181493] Other statin drugs impacted by this polymorphism include simvastatin, pitavastatin, rosuvastatin, and pravastatin.26

Volume of distribution

The reported volume of distribution of atorvastatin is of 380 L.39,40

Protein binding

Atorvastatin is highly bound to plasma proteins and over 98% of the administered dose is found in a bound form.39,40

Metabolism

Atorvastatin is highly metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products, primarily by Cytochrome P450 3A4 in the intestine and liver.39,40 Atorvastatin's metabolites undergo further lactonization via the formation of acyl glucuronide intermediates by the enzymes UGT1A1 and UGT1A3. These lactones can be hydrolyzed back to their corresponding acid forms and exist in equilibirum.5,26

In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites.39,40

Hover over products below to view reaction partners

Route of elimination

Atorvastatin and its metabolites are mainly eliminated in the bile without enterohepatic recirculation. The renal elimination of atorvastatin is very minimal and represents less than 1% of the eliminated dose.39,40

Half-life

The half-life of atorvastatin is 14 hours while the half-life of its metabolites can reach up to 30 hours.39,40

Clearance

The registered total plasma clearance of atorvastatin is of 625 ml/min.5

Adverse Effects
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Toxicity

The reported LD50 of oral atorvastatin in mice is higher than 5000 mg/kg.MSDS In cases of overdose with atorvastatin, there is reported symptoms of complicated breathing, jaundice, liver damage, dark urine, muscle pain, and seizures.37 In case of overdose, symptomatic treatment is recommended and due to the high plasma protein binding, hemodialysis is not expected to generate significant improvement.Label

In carcinogenic studies with high doses of atorvastatin, evidence of rhabdomyosarcoma, fibrosarcoma, liver adenoma, and liver carcinoma were observed.Label

In fertility studies with high doses of atorvastatin, there were events of aplasia, aspermia, low testis and epididymal weight, decreased sperm motility, decreased spermatid head concentration and increased abnormal sperm.Label

Atorvastatin was shown to not be mutagenic in diverse mutagenic assays.Label

Affected organisms
  • Humans and other mammals
Pathways
Not Available
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 atorvastatin.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 atorvastatin.Details
Cytochrome P450 3A4CYP3A4*1B(G;G) / (A;G)A > GEffect Directly StudiedPatients with this genotype have an greater reduction in LDL cholesterol with atorvastatin.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 Atorvastatin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Atorvastatin can be increased when combined with Abatacept.
AbirateroneThe metabolism of Atorvastatin can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Atorvastatin can be decreased when combined with Acalabrutinib.
AcenocoumarolThe risk or severity of bleeding can be increased when Atorvastatin is combined with Acenocoumarol.
AcetaminophenThe metabolism of Atorvastatin can be decreased when combined with Acetaminophen.
AcetazolamideThe metabolism of Atorvastatin can be decreased when combined with Acetazolamide.
AcetylcysteineThe excretion of Atorvastatin can be decreased when combined with Acetylcysteine.
AcipimoxAcipimox may increase the myopathic rhabdomyolysis activities of Atorvastatin.
AdalimumabThe metabolism of Atorvastatin can be increased when combined with Adalimumab.
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. Grapefruit products may increase the risk for atorvastatin related adverse effects such as myopathy and rhabdomyolysis.
  • Take with or without food. Food decreases absorption but not to a clinically significant extent.

Products

Product Ingredients
IngredientUNIICASInChI Key
Atorvastatin calciumC0GEJ5QCSO134523-03-8FQCKMBLVYCEXJB-MNSAWQCASA-L
Atorvastatin calcium trihydrate48A5M73Z4Q344423-98-9SHZPNDRIDUBNMH-NIJVSVLQSA-L
Product Images
International/Other Brands
Atogal (Ingers (Czech Republic)) / Cardyl (Pfizer (Spain)) / Faboxim (Fabop (Argentina)) / Hipolixan (Pasteur (Chile)) / Lipotropic (Drugtech (Chile)) / Liprimar (Pfizer (Hungary, Ukraine), Goedecke (Russia)) / Lowden (Saval (Chile)) / Normalip (Quesada (Argentina)) / Sincol (Indeco (Argentina)) / Sortis (Pfizer (Austria, Czech Republic, Germany, Hungary, Poland, Portugal, Switzerland), Godecke (Germany), Parke, Davis (Germany)) / Torvacard (Zentiva (Czech Republic, Hungary, Poland, Russia, Ukraine)) / Torvast (Pfizer (Italy)) / Totalip (Guidotti (Italy)) / Tulip (Lek (Czech Republic, Russia), Wermar (Mexico), Sandoz (Poland, Ukraine), Pharmacia (Spain)) / Vastina (Penn (Argentina)) / Xanator (Sieger (Greece)) / Xarator (Parke, Davis (Italy)) / Zurinel (Prater (Chile))
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AtorvastatinTabletOralLaboratoire Riva Inc2018-05-16Not applicableCanada flag
AtorvastatinTabletOralRatiopharm Inc Division Of Teva Canada Limited2010-05-192013-06-27Canada flag
AtorvastatinTabletOralSivem Pharmaceuticals Ulc2012-06-262018-10-17Canada flag
AtorvastatinTabletOralActavis Pharma CompanyNot applicableNot applicableCanada flag
AtorvastatinTabletOralSanis Health Inc2010-05-27Not applicableCanada flag
AtorvastatinTabletOralNora Pharma IncNot applicableNot applicableCanada flag
AtorvastatinTabletOralPro Doc Limitee2010-05-21Not applicableCanada flag
AtorvastatinTabletOralPharmascience Inc2013-03-26Not applicableCanada flag
AtorvastatinTabletOralRatiopharm Inc Division Of Teva Canada Limited2010-05-192013-06-27Canada flag
AtorvastatinTabletOralApotex Corporation2013-01-07Not 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
Ach-atorvastatin CalciumTabletOralAccord Healthcare Inc2019-10-18Not applicableCanada flag
Ach-atorvastatin CalciumTabletOralAccord Healthcare Inc2019-10-18Not applicableCanada flag
Ach-atorvastatin CalciumTabletOralAccord Healthcare Inc2019-10-18Not applicableCanada flag
Ach-atorvastatin CalciumTabletOralAccord Healthcare Inc2019-10-18Not applicableCanada flag
Ag-atorvastatinTabletOralAngita Pharma Inc.2018-09-27Not applicableCanada flag
Ag-atorvastatinTabletOralAngita Pharma Inc.2018-09-25Not applicableCanada flag
Ag-atorvastatinTabletOralAngita Pharma Inc.2018-09-25Not applicableCanada flag
Ag-atorvastatinTabletOralAngita Pharma Inc.2018-09-25Not applicableCanada flag
Apo-atorvastatinTabletOralApotex Corporation2010-05-19Not applicableCanada flag
Apo-atorvastatinTabletOralApotex Corporation2010-05-19Not 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
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (20 mg/1) + Amlodipine besylate (2.5 mg/1)Tablet, film coatedOralCadila Healthcare Limited2019-05-30Not applicableUS flag
Amlodipine and AtorvastatinAtorvastatin calcium trihydrate (10 mg/1) + Amlodipine besylate (5 mg/1)Tablet, film coatedOralApotex Corp.2020-07-29Not applicableUS flag
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (20 mg/1) + Amlodipine besylate (10 mg/1)Tablet, film coatedOralZydus Pharmaceuticals (USA) Inc.2019-05-30Not applicableUS flag
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (10 mg/1) + Amlodipine besylate (5 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.2015-04-02Not applicableUS flag
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (20 mg/1) + Amlodipine besylate (10 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.2014-02-11Not applicableUS flag
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (80 mg/1) + Amlodipine besylate (5 mg/1)Tablet, film coatedOralCadila Healthcare Limited2019-05-30Not applicableUS flag
Amlodipine and AtorvastatinAtorvastatin calcium trihydrate (20 mg/1) + Amlodipine besylate (10 mg/1)Tablet, film coatedOralApotex Corp.2020-07-29Not applicableUS flag
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (10 mg/1) + Amlodipine besylate (2.5 mg/1)Tablet, film coatedOralZydus Pharmaceuticals (USA) Inc.2019-05-30Not applicableUS flag
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (40 mg/1) + Amlodipine besylate (5 mg/1)Tablet, film coatedOralZydus Pharmaceuticals (USA) Inc.2019-05-30Not applicableUS flag
Amlodipine and atorvastatinAtorvastatin calcium trihydrate (10 mg/1) + Amlodipine besylate (2.5 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.2014-06-24Not applicableUS flag

Categories

ATC Codes
C10BX15 — Atorvastatin and perindoprilC10AA05 — AtorvastatinC10BX03 — Atorvastatin and amlodipineC10BA05 — Atorvastatin and ezetimibeC10BX11 — Atorvastatin, amlodipine and perindoprilC10BX08 — Atorvastatin and acetylsalicylic acidC10BX06 — Atorvastatin, acetylsalicylic acid and ramiprilC10BX12 — Atorvastatin, acetylsalicylic acid and perindopril
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as diphenylpyrroles. These are aromatic heterocyclic compounds with a structure based on a pyrrole ring linked to exactly two phenyl groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrroles
Sub Class
Substituted pyrroles
Direct Parent
Diphenylpyrroles
Alternative Parents
Aromatic anilides / Medium-chain hydroxy acids and derivatives / Pyrrole carboxamides / Medium-chain fatty acids / Beta hydroxy acids and derivatives / Fluorobenzenes / Halogenated fatty acids / Hydroxy fatty acids / Heterocyclic fatty acids / Aryl fluorides
show 13 more
Substituents
2,3-diphenylpyrrole / Alcohol / Aromatic anilide / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Beta-hydroxy acid / Carbonyl group
show 30 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
statin (synthetic), aromatic amide, pyrroles, dihydroxy monocarboxylic acid, monofluorobenzenes (CHEBI:39548)

Chemical Identifiers

UNII
A0JWA85V8F
CAS number
134523-00-5
InChI Key
XUKUURHRXDUEBC-KAYWLYCHSA-N
InChI
InChI=1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/t26-,27-/m1/s1
IUPAC Name
(3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid
SMILES
CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CC[[email protected]@H](O)C[[email protected]@H](O)CC(O)=O)C1=CC=C(F)C=C1)C1=CC=CC=C1

References

Synthesis Reference
US20020183527
General References
  1. Qiu S, Zhuo W, Sun C, Su Z, Yan A, Shen L: Effects of atorvastatin on chronic subdural hematoma: A systematic review. Medicine (Baltimore). 2017 Jun;96(26):e7290. doi: 10.1097/MD.0000000000007290. [PubMed:28658127]
  2. McIver LA, Siddique MS: Atorvastatin . [PubMed:28613530]
  3. Ye YC, Zhao XL, Zhang SY: Use of atorvastatin in lipid disorders and cardiovascular disease in Chinese patients. Chin Med J (Engl). 2015 Jan 20;128(2):259-66. doi: 10.4103/0366-6999.149226. [PubMed:25591572]
  4. Ray SK, Rege NN: Atorvastatin: in the management of hyperlipidaemia. J Postgrad Med. 2000 Jul-Sep;46(3):242-3. [PubMed:11298482]
  5. Lennernas H: Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. [PubMed:14531725]
  6. Lins RL, Matthys KE, Verpooten GA, Peeters PC, Dratwa M, Stolear JC, Lameire NH: Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients. Nephrol Dial Transplant. 2003 May;18(5):967-76. [PubMed:12686673]
  7. Zhao W, Zhao SP: Different effects of statins on induction of diabetes mellitus: an experimental study. Drug Des Devel Ther. 2015 Nov 24;9:6211-23. doi: 10.2147/DDDT.S87979. eCollection 2015. [PubMed:26648697]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. 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]
  21. Henwood JM, Heel RC: Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia. Drugs. 1988 Oct;36(4):429-54. doi: 10.2165/00003495-198836040-00003. [PubMed:3069436]
  22. Adams SP, Sekhon SS, Wright JM: Lipid-lowering efficacy of rosuvastatin. Cochrane Database Syst Rev. 2014 Nov 21;(11):CD010254. doi: 10.1002/14651858.CD010254.pub2. [PubMed:25415541]
  23. 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]
  24. 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]
  25. 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]
  26. 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]
  27. Bradford RH, Shear CL, Chremos AN, Dujovne CA, Franklin FA, Grillo RB, Higgins J, Langendorfer A, Nash DT, Pool JL, et al.: Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Am J Cardiol. 1994 Oct 1;74(7):667-73. doi: 10.1016/0002-9149(94)90307-7. [PubMed:7942524]
  28. Yahya R, Berk K, Verhoeven A, Bos S, van der Zee L, Touw J, Erhart G, Kronenberg F, Timman R, Sijbrands E, Roeters van Lennep J, Mulder M: Statin treatment increases lipoprotein(a) levels in subjects with low molecular weight apolipoprotein(a) phenotype. Atherosclerosis. 2019 Jul 3. pii: S0021-9150(19)31392-9. doi: 10.1016/j.atherosclerosis.2019.07.001. [PubMed:31327478]
  29. 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]
  30. Harper CR, Jacobson TA: The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr Opin Lipidol. 2007 Aug;18(4):401-8. doi: 10.1097/MOL.0b013e32825a6773. [PubMed:17620856]
  31. 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]
  32. Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, Moore R, Lee C, Chen Y, Schneck D: Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther. 2005 Oct;78(4):330-41. doi: 10.1016/j.clpt.2005.06.013. [PubMed:16198652]
  33. Corey E., Czako B. and Kurti L. (2007). Molecules and medicine. John Wiley & Sons, Inc. [ISBN:978-0-470-26096-8]
  34. Kumar R. and Bandichhor R. (2018). Hazardous reagent substitution. A pharmaceutical perspective. The Royal Society of Chemistry. [ISBN:978-1-78262-050-1]
  35. Merck Manuals [Link]
  36. Chemocare [Link]
  37. Laguna Treatment [Link]
  38. FDA Approved Drug Products: Lipitor (atorvastatin calcium) oral tablets [Link]
  39. FDA Label - Atorvastatin [File]
  40. Health Canada Monograph - Atorvastatin [File]
Human Metabolome Database
HMDB0005006
KEGG Drug
D07474
KEGG Compound
C06834
PubChem Compound
60823
PubChem Substance
46506188
ChemSpider
54810
BindingDB
22164
RxNav
1483793
ChEBI
39548
ChEMBL
CHEMBL1487
ZINC
ZINC000003920719
Therapeutic Targets Database
DAP000553
PharmGKB
PA448500
PDBe Ligand
117
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Atorvastatin
AHFS Codes
  • 24:06.08 — Hmg-coa Reductase Inhibitors
PDB Entries
1hwk
FDA label
Download (387 KB)
MSDS
Download (56.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingOtherAtherosclerosis / Carotid Artery Diseases / Coronary Artery Disease (CAD)1
4Active Not RecruitingPreventionAdverse Effects / Cardiovascular Heart Disease / Hyperlipidemias1
4Active Not RecruitingTreatmentChronic Kidney Disease (CKD)1
4Active Not RecruitingTreatmentDyslipidemia1
4CompletedNot AvailableAbdominal Aortic Aneurysms (AAA)1
4CompletedNot AvailableCardiovascular Heart Disease / Cholesterol, LDL / Cognition / Type 2 Diabetes Mellitus1
4CompletedNot AvailableChronic Stable Angina Pectoris / Coronary Heart Disease (CHD)1
4CompletedNot AvailableCoronary Heart Disease (CHD)1
4CompletedNot AvailableHealthy Volunteers3
4CompletedNot AvailableHigh Cholesterol4

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Bryant Ranch Prepack
  • Cardinal Health
  • Direct Pharmaceuticals Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Goedecke GmbH
  • Healthcare Pharmacy
  • Heartland Repack Services LLC
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Orifice Medical AB
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Tya Pharmaceuticals
  • US Pharmaceutical Group
  • Vangard Labs Inc.
  • Vitrum Ab
  • Warner Lambert Company LLC
Dosage Forms
FormRouteStrength
Tablet, film coated10 mg
Tablet, film coated20 mg
Tablet, film coated40 mg
Tablet80 mg
TabletOral
Tablet
Tablet, coatedOral2.5 mg
Tablet, coatedOral5 mg
Tablet, film coated80 mg
Capsule10 mg
Capsule20 mg
Tablet, coatedOral30 MG
Tablet, coatedOral60 MG
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, coatedOral21.65 mg
Tablet, film coatedOral10.825 mg
Tablet, film coatedOral
PowderNot applicable1 kg/1kg
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral40 mg/1
TabletOral80 mg/1
Tablet, film coatedOral10 mg/301
Tablet, film coatedOral20 mg/301
Tablet, film coatedOral80 mg/301
PowderNot applicable20 kg/20kg
TabletOral10 mg
Tablet, coatedOral20.7 mg
Tablet10 MG
TabletOral80 MG
Capsule, liquid filledOral10 mg
Capsule, liquid filledOral80 mg
Capsule, liquid filledOral43.376 mg
Tablet, coatedOral80 mg
Capsule, liquid filledOral20 mg
TabletOral
Tablet, film coatedOral
Tablet, coatedOral20 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral40 mg/1
Tablet, film coatedOral80 mg/1
TabletOral40 mg
Tablet, coatedOral10 mg
Capsule, liquid filledOral840 mg
Tablet, coatedOral40 mg
TabletOral20 mg
Tablet, chewableOral10 MG
Tablet, chewableOral20 MG
Tablet, chewableOral40 mg
Tablet, chewableOral5 mg
TabletOral5 MG
Tablet, coated10 MG
Tablet, coated20 MG
Tablet, coated40 MG
Tablet, coated80 MG
Prices
Unit descriptionCostUnit
Lipitor 20 mg tablet5.0USD tablet
Lipitor 40 mg tablet5.0USD tablet
Lipitor 80 mg tablet5.0USD tablet
Lipitor 10 mg tablet3.5USD tablet
Lipitor 40 mg Tablet2.52USD tablet
Lipitor 80 mg Tablet2.52USD tablet
Lipitor 20 mg Tablet2.34USD tablet
Lipitor 10 mg Tablet1.87USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US4681893No1987-07-212009-09-24US flag
CA2521776No2006-04-252022-05-21Canada flag
CA2220018No2001-04-172016-07-08Canada flag
US5969156Yes1999-10-192017-01-08US flag
USRE42461Yes2011-06-142017-04-25US flag
US6455574No2002-09-242018-08-11US 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)176 °C'MSDS'
boiling point (°C)722 ºC at 760 mmHg'MSDS'
water solubilityPractically insoluble'MSDS'
logP6.36'MSDS'
pKa4.46'MSDS'
Predicted Properties
PropertyValueSource
Water Solubility0.00063 mg/mLALOGPS
logP4.24ALOGPS
logP5.39ChemAxon
logS-6ALOGPS
pKa (Strongest Acidic)4.33ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area111.79 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity158.2 m3·mol-1ChemAxon
Polarizability59.39 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.8947
Blood Brain Barrier-0.7825
Caco-2 permeable-0.8956
P-glycoprotein substrateSubstrate0.5246
P-glycoprotein inhibitor IInhibitor0.7164
P-glycoprotein inhibitor IIInhibitor0.8724
Renal organic cation transporterNon-inhibitor0.8131
CYP450 2C9 substrateNon-substrate0.7887
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6841
CYP450 1A2 substrateNon-inhibitor0.8551
CYP450 2C9 inhibitorNon-inhibitor0.719
CYP450 2D6 inhibitorNon-inhibitor0.9042
CYP450 2C19 inhibitorNon-inhibitor0.6191
CYP450 3A4 inhibitorNon-inhibitor0.6675
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6894
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7777
BiodegradationNot ready biodegradable0.9974
Rat acute toxicity2.5686 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9904
hERG inhibition (predictor II)Non-inhibitor0.5101
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
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 , negativeLC-MS/MSsplash10-0a4i-0000090000-ae5c999b091a2bc93933
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a4i-0000190000-dd563e18b1f0f74aadd5
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0zfs-0007960000-cb66a18d2f0a687261ba
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-002b-0059000000-0942bc1e35434cd7d0d3
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-004i-0093000000-f42ba46820a3cf3295c5
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udj-0005910000-b09ba5f3b86948c7f3cb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0000090000-6f297ca79ae1761aac33
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0002-1009300000-9479520f395dcdd585e7
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-004i-0092000000-9b561b8d35c3bdc5e46a
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-004i-0090000000-3aad87273e7f9942a50f
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-01t9-1090000000-3f0efff41ebdb5320ce4
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-2090000000-0227638704b90c4249d0
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0a4i-0000090000-65c729c6734f6533c431
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0002-1009300000-9122e4479d8c0c32bb0d
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-004i-0092000000-22d639a8882509e1bcdb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-004i-0090000000-30a0198165bae85fa258
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-01t9-1090000000-cb3feea45f5280f05c37
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-03di-2090000000-8db2f70b373277f143c0
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0udj-0005910000-a63c845ca248d958068d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a6s-1085190000-9e43612012842effca5a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0031900000-4081fba1ae61b0d871cf
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-052f-0000980000-6751fefdee0a257e52f8
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0000900000-4009a70e947dcceb6e0f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0085900000-e1a4447e4c9a4bda83b2
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0092100000-4a5517154ad5f7375ea2
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000090000-e741fcb91eb29d1032cb
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00kf-0000900000-fdd41dae94afd3f4d3c5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000490000-25199beeece682c7de9e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0020900000-71cacdfc979c4386762b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0092000000-38374b1412250df34777
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0090000000-87710909ebad67c88f3b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udj-0190000000-60e7ef3dc3f76db11c5f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0f72-0290000000-e8c2cda8588874b2aaa5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000490000-a5ee6b466e73e9e72383
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0011900000-b8fc562d4be5ffb07f59
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0092000000-df78998b01951a3dd03a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0090000000-19c391db652668c97d59
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udj-0190000000-931a1911dcd7ec9dbbc8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0f72-0290000000-6157ef91cb98aeef5cf7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00kf-0000900000-cd6fb2c00146543cbb47
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f6x-0092420000-fb2c084ecdd5af8f6f7b

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. Davidson MH: Rosuvastatin: a highly efficacious statin for the treatment of dyslipidaemia. Expert Opin Investig Drugs. 2002 Mar;11(3):125-41. [PubMed:12769127]
  2. Jafari M, Ebrahimi R, Ahmadi-Kashani M, Balian H, Bashir M: Efficacy of alternate-day dosing versus daily dosing of atorvastatin. J Cardiovasc Pharmacol Ther. 2003 Jun;8(2):123-6. [PubMed:12808485]
  3. Baxter JD, Webb P, Grover G, Scanlan TS: Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight. Trends Endocrinol Metab. 2004 May-Jun;15(4):154-7. [PubMed:15109613]
  4. Maejima T, Yamazaki H, Aoki T, Tamaki T, Sato F, Kitahara M, Saito Y: Effect of pitavastatin on apolipoprotein A-I production in HepG2 cell. Biochem Biophys Res Commun. 2004 Nov 12;324(2):835-9. [PubMed:15474503]
  5. Bosel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, Megow D, Dirnagl U, Hortnagl H, Fink KB, Endres M: Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J Neurochem. 2005 Mar;92(6):1386-98. [PubMed:15748157]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by bindi...
Gene Name
DPP4
Uniprot ID
P27487
Uniprot Name
Dipeptidyl peptidase 4
Molecular Weight
88277.935 Da
References
  1. Taldone T, Zito SW, Talele TT: Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin. Bioorg Med Chem Lett. 2008 Jan 15;18(2):479-84. Epub 2007 Dec 3. [PubMed:18068977]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Transcription regulatory region dna binding
Specific Function
Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes...
Gene Name
AHR
Uniprot ID
P35869
Uniprot Name
Aryl hydrocarbon receptor
Molecular Weight
96146.705 Da
References
  1. Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. [PubMed:17327465]
  2. Chauvin B, Drouot S, Barrail-Tran A, Taburet AM: Drug-drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors. Clin Pharmacokinet. 2013 Oct;52(10):815-31. doi: 10.1007/s40262-013-0075-4. [PubMed:23703578]
  3. Korhonova M, Doricakova A, Dvorak Z: Optical Isomers of Atorvastatin, Rosuvastatin and Fluvastatin Enantiospecifically Activate Pregnane X Receptor PXR and Induce CYP2A6, CYP2B6 and CYP3A4 in Human Hepatocytes. PLoS One. 2015 Sep 14;10(9):e0137720. doi: 10.1371/journal.pone.0137720. eCollection 2015. [PubMed:26366873]
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]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Zinc ion binding
Specific Function
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name
NR1I3
Uniprot ID
Q14994
Uniprot Name
Nuclear receptor subfamily 1 group I member 3
Molecular Weight
39942.145 Da
References
  1. Rezen T, Hafner M, Kortagere S, Ekins S, Hodnik V, Rozman D: Rosuvastatin and Atorvastatin Are Ligands of the Human Constitutive Androstane Receptor/Retinoid X Receptor alpha Complex. Drug Metab Dispos. 2017 Aug;45(8):974-976. doi: 10.1124/dmd.117.075523. Epub 2017 May 23. [PubMed:28536098]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. [PubMed:11038166]
  5. Atorvastatin FDA Label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. [PubMed:11038166]
  2. Flockhart Table of Drug Interactions [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. [PubMed:11038166]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
  3. 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]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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. 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]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
Curator comments
Supporting data are limited to findings of an in vitro study.
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]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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. 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]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
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. Kobayashi K, Yamanaka Y, Iwazaki N, Nakajo I, Hosokawa M, Negishi M, Chiba K: Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9. Epub 2005 Mar 31. [PubMed:15802384]
  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
No
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. Stormo C, Bogsrud MP, Hermann M, Asberg A, Piehler AP, Retterstol K, Kringen MK: UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone. Mol Diagn Ther. 2013 Aug;17(4):233-7. doi: 10.1007/s40291-013-0031-x. [PubMed:23580084]
  2. Lennernas H: Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. [PubMed:14531725]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Stormo C, Bogsrud MP, Hermann M, Asberg A, Piehler AP, Retterstol K, Kringen MK: UGT1A1*28 is associated with decreased systemic exposure of atorvastatin lactone. Mol Diagn Ther. 2013 Aug;17(4):233-7. doi: 10.1007/s40291-013-0031-x. [PubMed:23580084]
  2. Lennernas H: Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. [PubMed:14531725]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. McIver LA, Siddique MS: Atorvastatin . [PubMed:28613530]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. 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]
  3. Lennernas H: Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. [PubMed:14531725]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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]
  2. Mandery K, Bujok K, Schmidt I, Keiser M, Siegmund W, Balk B, Konig J, Fromm MF, Glaeser H: Influence of the flavonoids apigenin, kaempferol, and quercetin on the function of organic anion transporting polypeptides 1A2 and 2B1. Biochem Pharmacol. 2010 Dec 1;80(11):1746-53. doi: 10.1016/j.bcp.2010.08.008. Epub 2010 Aug 24. [PubMed:20797388]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Lennernas H: Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. [PubMed:14531725]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. doi: 10.1161/CIRCRESAHA.109.203596. Epub 2009 Nov 25. [PubMed:19940267]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Acts as a multispecific organic anion pump which can transport nucleotide analogs.
Gene Name
ABCC5
Uniprot ID
O15440
Uniprot Name
Multidrug resistance-associated protein 5
Molecular Weight
160658.8 Da
References
  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. doi: 10.1161/CIRCRESAHA.109.203596. Epub 2009 Nov 25. [PubMed:19940267]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. doi: 10.1161/CIRCRESAHA.109.203596. Epub 2009 Nov 25. [PubMed:19940267]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Grube M, Kock K, Oswald S, Draber K, Meissner K, Eckel L, Bohm M, Felix SB, Vogelgesang S, Jedlitschky G, Siegmund W, Warzok R, Kroemer HK: Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clin Pharmacol Ther. 2006 Dec;80(6):607-20. [PubMed:17178262]
  2. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. doi: 10.1161/CIRCRESAHA.109.203596. Epub 2009 Nov 25. [PubMed:19940267]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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. Klatt S, Fromm MF, Konig J: The influence of oral antidiabetic drugs on cellular drug uptake mediated by hepatic OATP family members. Basic Clin Pharmacol Toxicol. 2013 Apr;112(4):244-50. doi: 10.1111/bcpt.12031. Epub 2012 Dec 6. [PubMed:23121773]
  2. Lennernas H: Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. [PubMed:14531725]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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]
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]

Drug created on June 13, 2005 07:24 / Updated on October 25, 2020 09:16

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