Atorvastatin 40mg/5ml oral solution
Prescription only
Requires a prescription from a doctor or prescriber
Oral solution
40mg/5ml
Oral
Atorvastatin (Lipitor®), is a lipid-lowering drug included in the statin class of medications.
Active ingredients:
Atorvastatin
1 safety notice
Genetic variations that may affect drug response
3 known genetic variations may influence how your body responds to Atorvastatin 40mg/5ml oral solution.Genes involved: KIF6, HMGCR, CYP3A4
These are known genetic variations. They don't mean the medicine won't work for you — speak to your doctor or a pharmacogenomics specialist for personalised advice. Source: DrugBank (CC BY-NC 4.0).
rs20455
KIF6
Patients with this genotype have a greater reduction in risk of a major cardiovascular event with high dose atorvastatin.
rs17244841
HMGCR
Patients with this genotype have a lesser reduction in LDL cholesterol with atorvastatin.
rs2740574
CYP3A4
Patients with this genotype have an greater reduction in LDL cholesterol with atorvastatin.
Official documents, adverse reaction reporting, and safety monitoring
Report a side effect
Submit a Yellow Card report to the MHRA
Official medicine documents
Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
Yellow Card reports
MHRA
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
View Drug Analysis Profile
Suspected adverse reactions reported for Atorvastatin
Browse all iDAP reports
Interactive Drug Analysis Profiles for all medicines
Report a side effect
Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
EMA
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
View EudraVigilance report
Suspected adverse reactions reported for Atorvastatin
About EudraVigilance
Learn about EU pharmacovigilance and safety monitoring
EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
1 branded products available
Show details
Show details
WHO defined daily dose (DDD)
20 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
Therapeutically similar medicines
Show details
Rosuvastatin 5mg orodispersible tablets sugar free
Tablet
5mg
Same therapeutic group
Rosuvastatin 10mg orodispersible tablets sugar free
Tablet
10mg
Same therapeutic group
Rosuvastatin 10mg/5ml oral solution sugar free
Oral solution
10mg/5ml
Same therapeutic group
Rosuvastatin 15mg tablets
Tablet
15mg
Same therapeutic group
Rosuvastatin 30mg tablets
Tablet
30mg
Same therapeutic group
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
Show details
Loading prescribing data...
Clinical guidelines and formulary information
British National Formulary
Atorvastatin
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(5)
Chronic kidney disease in adults (QS5)
QS5
Quality standard
Updated Jul 2017Cardiovascular disease: risk assessment and reduction, including lipid modification (NG238)
NG238
NICE guideline
Updated Dec 2023Cardiovascular risk assessment and lipid modification (QS100)
QS100
Quality standard
Updated Jul 2025Familial hypercholesterolaemia: identification and management (CG71)
CG71
Clinical guideline
Updated Oct 2019Familial hypercholesterolaemia (QS41)
QS41
Quality standard
Updated Nov 2017Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Show details
Pharmacy stock checkers
Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
Show details
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Show details
Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
72 found
Half-life
14 hours
Mechanism
Atorvastatin is a statin medication and a competitive inhibitor of the enzyme HM…
Food interactions
2 warnings
Human targets
5 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
40 mg
Atorvastatin presents a dose-dependent and non-linear pharmacokinetic profile.
[A177436]…
[A177436]…
Half-life
14 hours
The half-life of atorvastatin is 14 hours while the half-life of its metabolites can reach up to 30 hours.[F4670,F4673]
Protein binding
98%
Atorvastatin is highly bound to plasma proteins and over 98% of the administered dose is found in a bound form.[F4670,F4673]
Volume of distribution
380 L
The reported volume of distribution of atorvastatin is of 380 L.[F4670,F4673]
Metabolism
70%
Atorvastatin is highly metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products, primarily by Cytochrome P450 3A4 in the intestine and liver.[F4670,F4673]…
Elimination
1%
Atorvastatin and its metabolites are mainly eliminated in the bile without enterohepatic recirculation.…
Clearance
625 ml/min
The registered total plasma clearance of atorvastatin is of 625 ml/min.
[A19474]
[A19474]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
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,[A181421] 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.[A181087][A181406]
Atorvastatin and other statins including [lovastatin], [pravastatin], [rosuvastatin], [fluvastatin], and [simvastatin] are considered first-line treatment options for dyslipidemia.[A181087][A181406] 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.[A181084] An elevated cholesterol level (elevated low-density lipoprotein (LDL) levels in particular) is a significant risk factor for the development of CVD.[A181087][A181553] Several landmark studies demonstrate that the use of statins is associated with both a reduction in LDL levels and CVD risk.[A181090][A181093][A181096][A181427][A181475][A181538] 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.[A181087][A181406] 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.[A181397][A181403]
Atorvastatin was first synthesized in 1985 by Dr. Bruce Roth and approved by the FDA in 1996.T568 It is a pentasubstituted pyrrole [A177415] formed by two contrasting moieties with an achiral heterocyclic core unit and a 3,5-dihydroxypentanoyl side chain identical to its parent compound.T571 Unlike other members of the statin group, atorvastatin is an active compound and therefore does not require activation.[A177436]
Atorvastatin and other statins including [lovastatin], [pravastatin], [rosuvastatin], [fluvastatin], and [simvastatin] are considered first-line treatment options for dyslipidemia.[A181087][A181406] 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.[A181084] An elevated cholesterol level (elevated low-density lipoprotein (LDL) levels in particular) is a significant risk factor for the development of CVD.[A181087][A181553] Several landmark studies demonstrate that the use of statins is associated with both a reduction in LDL levels and CVD risk.[A181090][A181093][A181096][A181427][A181475][A181538] 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.[A181087][A181406] 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.[A181397][A181403]
Atorvastatin was first synthesized in 1985 by Dr. Bruce Roth and approved by the FDA in 1996.T568 It is a pentasubstituted pyrrole [A177415] formed by two contrasting moieties with an achiral heterocyclic core unit and a 3,5-dihydroxypentanoyl side chain identical to its parent compound.T571 Unlike other members of the statin group, atorvastatin is an active compound and therefore does not require activation.[A177436]
Properties:
View FDA drug labelsolid
Avg. mass: 558.64 Da
DrugBank 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.
[A177397]
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.
[L6025]
Atorvastatin is indicated, in combination with dietary modifications, to prevent cardiovascular events in patients with cardiac risk factors and/or abnormal lipid profiles.
[A177397]
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.
[A177397]
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.
[A177397]
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.
[A181087][A181406]
[A177397]
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.
[L6025]
Atorvastatin is indicated, in combination with dietary modifications, to prevent cardiovascular events in patients with cardiac risk factors and/or abnormal lipid profiles.
[A177397]
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.
[A177397]
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.
[A177397]
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.
[A181087][A181406]
Also known as(200)
Atorvastatin
atorvastatina
atorvastatine
atorvastatinum
1.1.1.34
HMG-CoA reductase
3.4.14.5
ADABP
Dosage forms(94)
Tablet (Oral) — 20 mg
Tablet (Oral) — 40 mg
Tablet (Oral) — 80 mg
Tablet (Oral) — 10.000 mg
Tablet, coated (Oral)
Tablet, film coated (Oral)
Tablet, film coated (Oral) — 30 MG
Tablet, film coated (Oral) — 60 MG
Molecular properties(19)
Drug interactions(765)
Known interactions with other medications. Always consult a healthcare professional.
Cyclosporine
Unknown severity
The excretion of Atorvastatin can be decreased when combined with Cyclosporine.
Reserpine may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Ursodeoxycholic acid
Moderate
Ursodeoxycholic acid may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Cholic Acid
Moderate
Cholic Acid may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Valinomycin
Moderate
Valinomycin may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Troglitazone
Moderate
Troglitazone may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Progesterone
Moderate
Progesterone may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Celecoxib may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Chlorpromazine
Moderate
Chlorpromazine may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Olmesartan
Moderate
Olmesartan may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Nifedipine
Moderate
Atorvastatin may decrease the excretion rate of Nifedipine which could result in a higher serum level.
Lenvatinib
Moderate
Lenvatinib may decrease the excretion rate of Atorvastatin which could result in a higher serum level.
Acipimox may increase the myopathic rhabdomyolysis activities of Atorvastatin.
Bezafibrate
Major
Bezafibrate may increase the myopathic rhabdomyolysis activities of Atorvastatin.
Ciprofibrate
Major
The risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Ciprofibrate is combined with Atorvastatin.
Daptomycin
Unknown severity
The risk or severity of myopathy can be increased when Atorvastatin is combined with Daptomycin.
Gemfibrozil
Major
The risk or severity of rhabdomyolysis, myoglobinuria, and elevated creatine kinase (CPK) can be increased when Gemfibrozil is combined with Atorvastatin.
The risk or severity of myopathy and rhabdomyolysis can be increased when Niacin is combined with Atorvastatin.
Raltegravir
Major
The risk or severity of myopathy and rhabdomyolysis can be increased when Raltegravir is combined with Atorvastatin.
Trabectedin
Major
The risk or severity of myopathy and rhabdomyolysis can be increased when Atorvastatin is combined with Trabectedin.
Fluconazole
Moderate
The metabolism of Atorvastatin can be decreased when combined with Fluconazole.
Erythromycin
Unknown severity
The serum concentration of Atorvastatin can be increased when it is combined with Erythromycin.
Azithromycin
Major
The risk or severity of myopathy and rhabdomyolysis can be increased when Azithromycin is combined with Atorvastatin.
The serum concentration of Atorvastatin can be decreased when it is combined with Bosentan.
The serum concentration of Atorvastatin can be increased when it is combined with Danazol.
The risk or severity of myopathy and rhabdomyolysis can be increased when Quinine is combined with Atorvastatin.
The risk or severity of myopathy and rhabdomyolysis can be increased when Quinidine is combined with Atorvastatin.
Ranolazine
Unknown severity
The serum concentration of Atorvastatin can be increased when it is combined with Ranolazine.
Bexarotene
Unknown severity
The serum concentration of Atorvastatin can be decreased when it is combined with Bexarotene.
The serum concentration of Diltiazem can be increased when it is combined with Atorvastatin.
Colestipol
Moderate
Colestipol can cause a decrease in the absorption of Atorvastatin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sevelamer can cause a decrease in the absorption of Atorvastatin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Colesevelam
Moderate
Colesevelam can cause a decrease in the absorption of Atorvastatin resulting in a reduced serum concentration and potentially a decrease in efficacy.
Cholestyramine
Moderate
Cholestyramine can cause a decrease in the absorption of Atorvastatin resulting in a reduced serum concentration and potentially a decrease in efficacy.
The serum concentration of Digoxin can be increased when it is combined with Atorvastatin.
Metildigoxin
Unknown severity
The serum concentration of Metildigoxin can be increased when it is combined with Atorvastatin.
Acetyldigoxin
Unknown severity
The serum concentration of Acetyldigoxin can be increased when it is combined with Atorvastatin.
Mifepristone
Unknown severity
The serum concentration of Atorvastatin can be increased when it is combined with Mifepristone.
The serum concentration of Verapamil can be increased when it is combined with Atorvastatin.
The serum concentration of Midazolam can be increased when it is combined with Atorvastatin.
Lamotrigine
Moderate
The metabolism of Atorvastatin can be increased when combined with Lamotrigine.
Desogestrel
Moderate
The metabolism of Atorvastatin can be increased when combined with Desogestrel.
Testosterone propionate
Moderate
The metabolism of Atorvastatin can be increased when combined with Testosterone propionate.
Tipranavir
Unknown severity
The serum concentration of Atorvastatin can be increased when it is combined with Tipranavir.
Telithromycin
Unknown severity
The serum concentration of Atorvastatin can be increased when it is combined with Telithromycin.
Ketoconazole
Unknown severity
The serum concentration of Atorvastatin can be increased when it is combined with Ketoconazole.
Isavuconazole
Moderate
The metabolism of Atorvastatin can be decreased when combined with Isavuconazole.
Abiraterone
Moderate
The metabolism of Atorvastatin can be decreased when combined with Abiraterone.
Dabrafenib
Moderate
The metabolism of Atorvastatin can be decreased when combined with Dabrafenib.
The metabolism of Atorvastatin can be decreased when combined with Etoposide.
Showing 50 of 765 interactions
Food & lifestyle interactions
Avoid Grapefruit
Avoid grapefruit products. Grapefruit products may increase the risk for atorvastatin related adverse effects such as myopathy and rhabdomyolysis.
Advice
Take with or without food. Food decreases absorption but not to a clinically significant extent.
Toxicity & overdose
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.
[L6031]
In case of overdose, symptomatic treatment is recommended and due to the high plasma protein binding, hemodialysis is not expected to generate significant improvement.[FDA label]
In carcinogenic studies with high doses of atorvastatin, evidence of rhabdomyosarcoma, fibrosarcoma, liver adenoma, and liver carcinoma were observed.[FDA 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.[FDA label]
Atorvastatin was shown to not be mutagenic in diverse mutagenic assays.[FDA label]
[L6031]
In case of overdose, symptomatic treatment is recommended and due to the high plasma protein binding, hemodialysis is not expected to generate significant improvement.[FDA label]
In carcinogenic studies with high doses of atorvastatin, evidence of rhabdomyosarcoma, fibrosarcoma, liver adenoma, and liver carcinoma were observed.[FDA 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.[FDA label]
Atorvastatin was shown to not be mutagenic in diverse mutagenic assays.[FDA label]
How it works
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.[A177388][A181421] 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.[A181424] 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.[A181559]
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.[A181424] 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.[A181559]
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.[A174580][A181087][A181406][A181925]
Elevated cholesterol levels (and high low-density lipoprotein (LDL) levels in particular) are an important risk factor for the development of CVD.[A181087] Clinical studies have shown that atorvastatin reduces LDL-C and total cholesterol by 36-53%.[A177415] In patients with dysbetalipoproteinemia, atorvastatin reduced the levels of intermediate-density lipoprotein cholesterol.[A177397] It has also been suggested that atorvastatin can limit the extent of angiogenesis, which can be useful in the treatment of chronic subdural hematoma.[A177388]
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.[A182258]
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.[F4670,F4673]
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.[A182012]
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.F4673
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.F4673
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.F4673 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.[A181418]
Elevated cholesterol levels (and high low-density lipoprotein (LDL) levels in particular) are an important risk factor for the development of CVD.[A181087] Clinical studies have shown that atorvastatin reduces LDL-C and total cholesterol by 36-53%.[A177415] In patients with dysbetalipoproteinemia, atorvastatin reduced the levels of intermediate-density lipoprotein cholesterol.[A177397] It has also been suggested that atorvastatin can limit the extent of angiogenesis, which can be useful in the treatment of chronic subdural hematoma.[A177388]
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.[A182258]
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.[F4670,F4673]
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.[A182012]
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.F4673
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.F4673
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.F4673 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.[A181418]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Atorvastatin presents a dose-dependent and non-linear pharmacokinetic profile.
[A177436]
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.
[A177478]
Atorvastatin undergoes extensive first-pass metabolism in the wall of the gut and the liver, resulting in an absolute oral bioavailability of 14%.
[A177397]
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.F4670
Administration of atorvastatin with food results in prolonged Tmax and a reduction in Cmax and AUC.
[A177415]
Breast Cancer Resistance Protein (BCRP) is a membrane-bound protein that plays an important role in the absorption of atorvastatin.
[A181460]
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.
[A181478][A181487]
Other statin drugs impacted by this polymorphism include [fluvastatin], [simvastatin], and [rosuvastatin].
[A181478]
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].
[A181460]
[A177436]
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.
[A177478]
Atorvastatin undergoes extensive first-pass metabolism in the wall of the gut and the liver, resulting in an absolute oral bioavailability of 14%.
[A177397]
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.F4670
Administration of atorvastatin with food results in prolonged Tmax and a reduction in Cmax and AUC.
[A177415]
Breast Cancer Resistance Protein (BCRP) is a membrane-bound protein that plays an important role in the absorption of atorvastatin.
[A181460]
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.
[A181478][A181487]
Other statin drugs impacted by this polymorphism include [fluvastatin], [simvastatin], and [rosuvastatin].
[A181478]
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].
[A181460]
Half-life
The half-life of atorvastatin is 14 hours while the half-life of its metabolites can reach up to 30 hours.[F4670,F4673]
Protein binding
Atorvastatin is highly bound to plasma proteins and over 98% of the administered dose is found in a bound form.[F4670,F4673]
Volume of distribution
The reported volume of distribution of atorvastatin is of 380 L.[F4670,F4673]
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.[F4670,F4673] 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.
[A19474][A181460]
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.[F4670,F4673]
[A19474][A181460]
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.[F4670,F4673]
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.[F4670,F4673]
Clearance
The registered total plasma clearance of atorvastatin is of 625 ml/min.
[A19474]
[A19474]
Drug targets(5)
Proteins and enzymes this drug interacts with in the body
3-hydroxy-3-methylglutaryl-coenzyme A reductase
HMGCR
inhibitor
Specific functioncoenzyme A binding
Cellular location
Endoplasmic reticulum membrane
General function & pharmacology
Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis .
PMID:21357570 PMID:2991281 PMID:36745799 PMID:6995544
HMGCR is the main target of statins, a class of cholesterol-lowering drugs PMID:11349148 PMID:18540668 PMID:36745799
PMID:21357570 PMID:2991281 PMID:36745799 PMID:6995544
HMGCR is the main target of statins, a class of cholesterol-lowering drugs PMID:11349148 PMID:18540668 PMID:36745799
Dipeptidyl peptidase 4
DPP4
inhibitor
Specific functionaminopeptidase activity
Cellular location
Secreted
General function & pharmacology
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation .
PMID:10900005 PMID:10951221 PMID:11772392 PMID:17287217
Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC .
PMID:10900005 PMID:10951221 PMID:11772392 PMID:14691230
Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner .
PMID:17287217
Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion .
PMID:11772392
In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM .
PMID:10593948 PMID:16651416
May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation .
PMID:18708048
When overexpressed, enhanced cell proliferation, a process inhibited by GPC3 .
PMID:17549790
Also acts as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones such as brain natriuretic peptide 32 .
PMID:10570924 PMID:16254193
Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline PMID:10593948
PMID:10900005 PMID:10951221 PMID:11772392 PMID:17287217
Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC .
PMID:10900005 PMID:10951221 PMID:11772392 PMID:14691230
Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner .
PMID:17287217
Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion .
PMID:11772392
In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM .
PMID:10593948 PMID:16651416
May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation .
PMID:18708048
When overexpressed, enhanced cell proliferation, a process inhibited by GPC3 .
PMID:17549790
Also acts as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones such as brain natriuretic peptide 32 .
PMID:10570924 PMID:16254193
Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline PMID:10593948
Aryl hydrocarbon receptor
AHR
agonist
Specific functioncis-regulatory region sequence-specific DNA binding
Cellular location
Cytoplasm
General function & pharmacology
Ligand-activated transcription factor that enables cells to adapt to changing conditions by sensing compounds from the environment, diet, microbiome and cellular metabolism, and which plays important roles in development, immunity and cancer .
PMID:23275542 PMID:30373764 PMID:32818467 PMID:7961644
Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) .
PMID:23275542 PMID:30373764 PMID:7961644
Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation .
PMID:12213388
Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) .
PMID:7961644 PMID:33193710
Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons .
PMID:34521881 PMID:7961644
Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists .
PMID:18076143
Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands .
PMID:32818467 PMID:32866000
Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity .
PMID:32818467
Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 .
PMID:28602820
Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 .
PMID:28602820
The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription PMID:28602820
PMID:23275542 PMID:30373764 PMID:32818467 PMID:7961644
Upon ligand binding, translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE) .
PMID:23275542 PMID:30373764 PMID:7961644
Regulates a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation .
PMID:12213388
Xenobiotics can act as ligands: upon xenobiotic-binding, activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene) .
PMID:7961644 PMID:33193710
Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons .
PMID:34521881 PMID:7961644
Next to xenobiotics, natural ligands derived from plants, microbiota, and endogenous metabolism are potent AHR agonists .
PMID:18076143
Tryptophan (Trp) derivatives constitute an important class of endogenous AHR ligands .
PMID:32818467 PMID:32866000
Acts as a negative regulator of anti-tumor immunity: indoles and kynurenic acid generated by Trp catabolism act as ligand and activate AHR, thereby promoting AHR-driven cancer cell motility and suppressing adaptive immunity .
PMID:32818467
Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1 .
PMID:28602820
Inhibits PER1 by repressing the CLOCK-BMAL1 heterodimer mediated transcriptional activation of PER1 .
PMID:28602820
The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription PMID:28602820
Histone deacetylase 2
HDAC2
inhibitor
Specific functionchromatin binding
Cellular location
Nucleus
General function & pharmacology
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) .
PMID:28497810
Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR .
PMID:12724404
Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (By similarity).
Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin .
PMID:16428440 PMID:28977666
Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 .
PMID:37137925
Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity .
PMID:19343227
May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (By similarity). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A .
PMID:21965678
In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively PMID:28497810 PMID:29192674 PMID:35044827
PMID:28497810
Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR .
PMID:12724404
Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (By similarity).
Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin .
PMID:16428440 PMID:28977666
Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 .
PMID:37137925
Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity .
PMID:19343227
May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (By similarity). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A .
PMID:21965678
In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively PMID:28497810 PMID:29192674 PMID:35044827
Nuclear receptor subfamily 1 group I member 3
NR1I3
ligand
Specific functionDNA-binding transcription activator activity, RNA polymerase II-specific
Cellular location
Nucleus
General function & pharmacology
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 responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element
Metabolizing enzymes(10)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP3A4Cytochrome P450 3A4
substrate
CYP3A5Cytochrome P450 3A5
substrate
CYP3A7Cytochrome P450 3A7
substrate
CYP2C8Cytochrome P450 2C8
substrate
inhibitor
CYP2D6Cytochrome P450 2D6
inhibitor
CYP2C9Cytochrome P450 2C9
inhibitor
CYP2C19Cytochrome P450 2C19
inhibitor
CYP2B6Cytochrome P450 2B6
inducer
UGT1A1UDP-glucuronosyltransferase 1A1
substrate
UGT1A3UDP-glucuronosyltransferase 1A3
substrate
Transporters(10)
Proteins that transport this drug across cell membranes
ATP-dependent translocase ABCB1
ABCB1
substrate
inhibitor
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Solute carrier organic anion transporter family member 1A2
SLCO1A2
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane .
PMID:19129463 PMID:7557095
Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) .
PMID:11159893 PMID:12568656 PMID:19129463 PMID:23918469 PMID:25560245 PMID:9539145
Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision .
PMID:25560245
Involved in the uptake of clinically used drugs .
PMID:17301733 PMID:20686826 PMID:27777271
Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) .
PMID:19129463 PMID:20358049
Also transports prostaglandin E2 .
PMID:19129463
Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
PMID:19129463 PMID:7557095
Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) .
PMID:11159893 PMID:12568656 PMID:19129463 PMID:23918469 PMID:25560245 PMID:9539145
Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision .
PMID:25560245
Involved in the uptake of clinically used drugs .
PMID:17301733 PMID:20686826 PMID:27777271
Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) .
PMID:19129463 PMID:20358049
Also transports prostaglandin E2 .
PMID:19129463
Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Solute carrier organic anion transporter family member 1B1
SLCO1B1
substrate
inhibitor
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
ATP-binding cassette sub-family C member 4
ABCC4
substrate
Specific function15-hydroxyprostaglandin dehydrogenase (NAD+) activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins .
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
ATP-binding cassette sub-family C member 5
ABCC5
substrate
Specific functionABC-type xenobiotic transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) .
PMID:10893247 PMID:12637526 PMID:12695538 PMID:15899835 PMID:17229149 PMID:25964343
Also acts as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins .
PMID:26515061
Confers resistance to the antiviral agent PMEA .
PMID:12695538
Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated .
PMID:10840050 PMID:12435799 PMID:12695538 PMID:15899835
Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway .
PMID:24836561
May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity)
PMID:10893247 PMID:12637526 PMID:12695538 PMID:15899835 PMID:17229149 PMID:25964343
Also acts as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins .
PMID:26515061
Confers resistance to the antiviral agent PMEA .
PMID:12695538
Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated .
PMID:10840050 PMID:12435799 PMID:12695538 PMID:15899835
Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway .
PMID:24836561
May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity)
Multidrug resistance-associated protein 1
ABCC1
substrate
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Cell membrane
General function & pharmacology
Mediates export of organic anions and drugs from the cytoplasm .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export .
PMID:9281595
Hydrolyzes ATP with low efficiency .
PMID:16230346
Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation .
PMID:17050692
Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export .
PMID:36070769
Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway .
PMID:36070769
Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity).
Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells PMID:9426231
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export .
PMID:9281595
Hydrolyzes ATP with low efficiency .
PMID:16230346
Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation .
PMID:17050692
Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export .
PMID:36070769
Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway .
PMID:36070769
Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity).
Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells PMID:9426231
Solute carrier organic anion transporter family member 2B1
SLCO2B1
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions .
PMID:10873595 PMID:11159893 PMID:11932330 PMID:12724351 PMID:14610227 PMID:16908597 PMID:18501590 PMID:20507927 PMID:22201122 PMID:23531488 PMID:25132355 PMID:26383540 PMID:27576593 PMID:28408210 PMID:29871943 PMID:34628357
Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) .
PMID:11932330 PMID:12409283
Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver .
PMID:11159893
Mediates the intestinal uptake of sulfated steroids .
PMID:12724351 PMID:28408210
Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain .
PMID:16908597 PMID:25132355
Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC .
PMID:35714613
Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition .
PMID:26383540
Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:14610227 PMID:19129463 PMID:22201122
The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound .
PMID:19129463 PMID:20507927 PMID:26277985
Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions .
PMID:19129463
Cytoplasmic glutamate may also act as counteranion in the placenta .
PMID:26277985
An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) PMID:20507927
PMID:10873595 PMID:11159893 PMID:11932330 PMID:12724351 PMID:14610227 PMID:16908597 PMID:18501590 PMID:20507927 PMID:22201122 PMID:23531488 PMID:25132355 PMID:26383540 PMID:27576593 PMID:28408210 PMID:29871943 PMID:34628357
Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) .
PMID:11932330 PMID:12409283
Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver .
PMID:11159893
Mediates the intestinal uptake of sulfated steroids .
PMID:12724351 PMID:28408210
Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain .
PMID:16908597 PMID:25132355
Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC .
PMID:35714613
Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition .
PMID:26383540
Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:14610227 PMID:19129463 PMID:22201122
The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound .
PMID:19129463 PMID:20507927 PMID:26277985
Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions .
PMID:19129463
Cytoplasmic glutamate may also act as counteranion in the placenta .
PMID:26277985
An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) PMID:20507927
Solute carrier organic anion transporter family member 1B3
SLCO1B3
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
ATP-binding cassette sub-family C member 2
ABCC2
substrate
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Apical cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates .
PMID:10220572 PMID:10421658 PMID:11500505 PMID:16332456
Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification .
PMID:10421658
Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 .
PMID:11500505
Transports sulfated bile salt such as taurolithocholate sulfate .
PMID:16332456
Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors .
PMID:10220572 PMID:11500505 PMID:12441801
Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine PMID:10220572 PMID:11500505
PMID:10220572 PMID:10421658 PMID:11500505 PMID:16332456
Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification .
PMID:10421658
Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 .
PMID:11500505
Transports sulfated bile salt such as taurolithocholate sulfate .
PMID:16332456
Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors .
PMID:10220572 PMID:11500505 PMID:12441801
Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine PMID:10220572 PMID:11500505
Bile salt export pump
ABCB11
substrate
Specific functionABC-type bile acid transporter activity
Cellular location
Apical cell membrane
General function & pharmacology
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner .
PMID:15791618 PMID:16332456 PMID:18985798 PMID:19228692 PMID:20010382 PMID:20398791 PMID:22262466 PMID:24711118 PMID:29507376 PMID:32203132
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts .
PMID:16332456
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion PMID:15901796 PMID:18245269
PMID:15791618 PMID:16332456 PMID:18985798 PMID:19228692 PMID:20010382 PMID:20398791 PMID:22262466 PMID:24711118 PMID:29507376 PMID:32203132
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts .
PMID:16332456
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion PMID:15901796 PMID:18245269
Carriers(1)
Proteins that carry this drug through the body
Albumin
ALB
binder
Specific functionantioxidant activity
Cellular location
Secreted
General function & pharmacology
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc .
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
Scientific references(33)
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 Jun96(26):e7290. doi: 10.1097/MD.0000000000007290
McIver L.A., Siddique M.S.
A One-step Sample Processing Method in Combination With Hplc-Ms/Ms for the Simultaneous Quantification of Atorvastatin, Ezetimibe and Three Metabolites Including O-Hydroxyl Atorvastatin, P-Hydroxyl Atorvastatin, and Ezetimibe-Glucuronide in Human Plasma. doi: 10.20944/preprints202306.
1548
v1
Ye Y.C., Zhao X.L., Zhang S.Y.
Use of atorvastatin in lipid disorders and cardiovascular disease in Chinese patients.
Chin Medicine Journal (Engl)
2015 Jan 20128(2):259-66. doi: 10.4103/0366-6999.149226
Ray S.K., Rege N.N.
GATR Journal of Management and Marketing Review. 4. doi: 10.35609/jmmr.
2019
4
Lennernas H.
Clinical Pharmacokinetics of Atorvastatin.
Clinical Pharmacokinetics
200342(13):1141-1160. doi: 10.2165/00003088-200342130-00005
Lins R.L., Matthys K.E., Verpooten G.A., Peeters P.C., Dratwa M., Stolear J.C., Lameire N.H.
Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients.
Nephrology Dialysis Transplantation
200318(5):967-976. doi: 10.1093/ndt/gfg048
Zhao W., Zhao S.P.
Different effects of statins on induction of diabetes mellitus: an experimental study.
Drug Des Devel Therapeutics
2015 Nov 249:6211-23. doi: 10.2147/DDDT.S87979. eCollection 2015
Moghadasian M.H.
Clinical pharmacology of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
Life Science
199965(13):1329-37. doi: 10.1016/s0024-3205(99)00199-x
Anderson T.J., Gregoire J., Pearson G.J., Barry A.R., Couture P., Dawes M., Francis G.A., Genest J Jr, Grover S., Gupta M., Hegele R.A., Lau D.C., Leiter L.A., Lonn E., Mancini G.B., McPherson R., Ngui D., Poirier P., Sievenpiper J.L., Stone J.A., Thanassoulis G., Ward R.
2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult.
Can Journal Cardiology
2016 Nov32(11):1263-1282. doi: 10.1016/j.cjca.2016.07.510. Epub 2016 Jul 25
Grundy S.M., Stone N.J.
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
Kreatsoulas C., Anand S.S.
The impact of social determinants on cardiovascular disease.
Can Journal Cardiology
2010 Aug-Sep26 Suppl C:8C-13C. doi: 10.1016/s0828-282x(10)71075-8
Kannel W.B., Castelli W.P., Gordon T., McNamara P.M.
Serum cholesterol, lipoproteins, and the risk of coronary heart disease.
The Framingham study
Ann Intern Med. 1971 Jan74(1):1-12. doi: 10.7326/0003-4819-74-1-1
Authors unspecified
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.
New England Journal of Medicine
1998 Nov 5339(19):1349-57. doi: 10.1056/NEJM199811053391902
Cannon C.P., Braunwald E., McCabe C.H., Rader D.J., Rouleau J.L., Belder R., Joyal S.V., Hill K.A., Pfeffer M.A., Skene A.M.
Intensive versus moderate lipid lowering with statins after acute coronary syndromes.
New England Journal of Medicine
2004 Apr 8350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8
Ridker P.M., Danielson E., Fonseca F.A., Genest J., Gotto AM Jr, Kastelein J.J., Koenig W., Libby P., Lorenzatti A.J., MacFadyen J.G., Nordestgaard B.G., Shepherd J., Willerson J.T., Glynn R.J.
Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
New England Journal of Medicine
2008 Nov 20359(21):2195-207. doi: 10.1056/NEJMoa0807646. Epub 2008 Nov 9
Nicholls S.J., Ballantyne C.M., Barter P.J., Chapman M.J., Erbel R.M., Libby P., Raichlen J.S., Uno K., Borgman M., Wolski K., Nissen S.E.
Effect of two intensive statin regimens on progression of coronary disease.
New England Journal of Medicine
2011 Dec 1365(22):2078-87. doi: 10.1056/NEJMoa1110874. Epub 2011 Nov 15
Authors unspecified
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.
The Lancet
2002 Jul 6360(9326):7-22. doi: 10.1016/S0140-6736(02)09327-3
Authors unspecified
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).
The Lancet
1994344(8934). doi: 10.1016/s0140-6736(94)90566-5
Mihaylova B., Emberson J., Blackwell L., Keech A., Simes J., Barnes E.H., 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.
The Lancet
2012 Aug 11380(9841):581-90. doi: 10.1016/S0140-6736(12)60367-5. Epub 2012 May 17
Taylor F., Huffman M.D., Macedo A.F., Moore T.H., Burke M., Davey Smith G., Ward K., Ebrahim S.
Statins for the primary prevention of cardiovascular disease.
Cochrane Database of Systematic Reviews
2013 Jan 31(1):CD004816. doi: 10.1002/14651858.CD004816.pub5
ATC classification(10 codes)
ATC C10BA05
ATC C10BX11
ATC C10BX12
ATC C10BX19
ATC C10BX18
ATC C10AA05
ATC C10BX15
ATC C10BX03
ATC C10BX08
ATC C10BX06
Affected organisms(1)
Humans and other mammals
International brands(18)
Salt forms(2)
Atorvastatin calcium(DBSALT000011)
Atorvastatin calcium trihydrate(DBSALT001499)
Experimental properties(5)
Protein Data Bank entries(1)
Commercial products(1321)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Atorvastatin
Additional database identifiers
Drugs Product Database (DPD)
11366
ChemSpider
54810
BindingDB
22164
PDB
117
ZINC
ZINC000003920719
HUGO Gene Nomenclature Committee (HGNC)
HGNC:5006
GenAtlas
HMGCR
GeneCards
HMGCR
GenBank Gene Database
M11058
GenBank Protein Database
306865
Guide to Pharmacology
639
UniProt Accession
HMDH_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3009
GenAtlas
DPP4
GeneCards
DPP4
GenBank Gene Database
U13735
GenBank Protein Database
535388
Guide to Pharmacology
1612
UniProt Accession
DPP4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:348
GeneCards
AHR
GenBank Gene Database
D16354
GenBank Protein Database
533324
Guide to Pharmacology
2951
UniProt Accession
AHR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4853
GenAtlas
HDAC2
GeneCards
HDAC2
GenBank Gene Database
U31814
GenBank Protein Database
1667394
Guide to Pharmacology
2616
UniProt Accession
HDAC2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7969
GeneCards
NR1I3
GenBank Gene Database
Z30425
GenBank Protein Database
458542
Guide to Pharmacology
607
UniProt Accession
NR1I3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2638
GenAtlas
CYP3A5
GeneCards
CYP3A5
GenBank Gene Database
J04813
GenBank Protein Database
181346
Guide to Pharmacology
1338
UniProt Accession
CP3A5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2640
GeneCards
CYP3A7
GenBank Gene Database
D00408
GenBank Protein Database
220149
UniProt Accession
CP3A7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2622
GenAtlas
CYP2C8
GeneCards
CYP2C8
GenBank Gene Database
M17397
Guide to Pharmacology
1325
UniProt Accession
CP2C8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2625
GenAtlas
CYP2D6
GeneCards
CYP2D6
GenBank Gene Database
M20403
GenBank Protein Database
181350
Guide to Pharmacology
1329
UniProt Accession
CP2D6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12530
GeneCards
UGT1A1
GenBank Gene Database
M57899
GenBank Protein Database
184473
Guide to Pharmacology
2990
UniProt Accession
UD11_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12535
GeneCards
UGT1A3
GenBank Gene Database
M84127
GenBank Protein Database
340135
UniProt Accession
UD13_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10956
GeneCards
SLCO1A2
GenBank Gene Database
U21943
GenBank Protein Database
885978
Guide to Pharmacology
1219
UniProt Accession
SO1A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10959
GenAtlas
SLCO1B1
GeneCards
SLCO1B1
GenBank Gene Database
AF060500
GenBank Protein Database
5051630
Guide to Pharmacology
1220
UniProt Accession
SO1B1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:55
GenAtlas
ABCC4
GeneCards
ABCC4
GenBank Gene Database
AF071202
GenBank Protein Database
3335173
Guide to Pharmacology
782
UniProt Accession
MRP4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:56
GeneCards
ABCC5
GenBank Gene Database
AF104942
GenBank Protein Database
4140698
Guide to Pharmacology
783
UniProt Accession
MRP5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:51
GenAtlas
ABCC1
GeneCards
ABCC1
GenBank Gene Database
L05628
GenBank Protein Database
1835659
Guide to Pharmacology
779
UniProt Accession
MRP1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10962
GenAtlas
SLCO2B1
GeneCards
SLCO2B1
GenBank Gene Database
AB026256
GenBank Protein Database
5006263
Guide to Pharmacology
1224
UniProt Accession
SO2B1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10961
GeneCards
SLCO1B3
GenBank Gene Database
AJ251506
GenBank Protein Database
9187497
Guide to Pharmacology
1221
UniProt Accession
SO1B3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:53
GenAtlas
ABCC2
GeneCards
ABCC2
GenBank Gene Database
U63970
GenBank Protein Database
1764162
Guide to Pharmacology
780
UniProt Accession
MRP2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:42
GenAtlas
ABCB11
GeneCards
ABCB11
GenBank Gene Database
AF091582
GenBank Protein Database
3873243
Guide to Pharmacology
778
UniProt Accession
ABCBB_HUMAN
International reference pricing
8 formulations
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
From $1.87/tablet
To $5.00/tablet
Lipitor 10 mg Tablet
$1.87/tablet
Lipitor 20 mg Tablet
$2.34/tablet
Lipitor 40 mg Tablet
$2.52/tablet
Lipitor 80 mg Tablet
$2.52/tablet
Lipitor 10 mg tablet
$3.50/tablet
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
5 active patents, 6 expired
11369567
United States
Approved 28 Jun 2022 · Expires 7 Jun 2037
11y 2m
11654106
United States
Approved 23 May 2023 · Expires 7 Jun 2037
11y 2m
11925704
United States
Approved 12 Mar 2024 · Expires 7 Jun 2037
11y 2m
12168069
United States
Approved 17 Dec 2024 · Expires 7 Jun 2037
11y 2m
12370136
United States
Approved 7 Jun 2017 · Expires 7 Jun 2037
11y 2m
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated 27 days ago(8 Mar 2026)