ATORVASTATIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H35FN2O5
Molecular Weight	558.6398
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CC[C@@H](O)C[C@@H](O)CC(O)=O)C3=CC=C(F)C=C3)C4=CC=CC=C4

InChI

InChIKey=XUKUURHRXDUEBC-KAYWLYCHSA-N

InChI=1S/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/t26-,27-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C33H35FN2O5
Molecular Weight	558.6398
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020702s065lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/2009919

Atorvastatin calcium (LIPITOR®) is a pyrrole and heptanoic acid derivative, a synthetic lipid-lowering agent. Atorvastatin is a selective, competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in cholesterol biosynthesis. Atorvastatin is used to reduce serum levels of LDL(low-density lipoprotein)-cholesterol; apolipoprotein B; and triglycerides and to increase serum levels of HDL(high-density lipoprotein)-cholesterol in the treatment of hyperlipidemias and prevention of cardiovascular disease in patients with multiple risk factors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020702s065lbl.pdf	Inhibitor 8297		14.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cardiovascular diseases 71 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020702s065lbl.pdf	Preventing		Approved 8429	LIPITOR Approved Use Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with CHD or multiple risk factors for CHD, atorvastatin calcium tablets can be started simultaneously with diet. Atorvastatin calcium tablets are an inhibitor of HMG-CoA reductase (statin) indicated as an adjunct therapy to diet to: Reduce the risk of MI, stroke, revascularization procedures, and angina in patients without CHD, but with multiple risk factors (1.1). Reduce the risk of MI and stroke in patients with type 2 diabetes without CHD, but with multiple risk factors (1.1). Reduce the risk of non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for CHF, and angina in patients with CHD (1.1). Reduce elevated total-C, LDL-C, apo B, and TG levels and increase HDL-C in adult patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (1.2). Reduce elevated TG in patients with hypertriglyceridemia and primary dysbetalipoproteinemia (1.2). Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH) (1.2). Reduce elevated total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.2). Limitations of Use Atorvastatin calcium tablets have not been studied in Fredrickson Types I and V dyslipidemias. 1.1 Prevention of Cardiovascular Disease In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL-C, or a family history of early coronary heart disease, atorvastatin calcium tablets are indicated to: Reduce the risk of myocardial infarction Reduce the risk of stroke Reduce the risk for revascularization procedures and angina In patients with type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension, atorvastatin calcium tablets are indicated to: Reduce the risk of myocardial infarction Reduce the risk of stroke In patients with clinically evident coronary heart disease, atorvastatin calcium tablets are indicated to: Reduce the risk of non-fatal myocardial infarction Reduce the risk of fatal and non-fatal stroke Reduce the risk for revascularization procedures Reduce the risk of hospitalization for CHF Reduce the risk of angina 1.2 Hyperlipidemia Atorvastatin calcium tablets are indicated: As an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia ( Types IIa and IIb); Fredrickson As an adjunct to diet for the treatment of patients with elevated serum TG levels ( Type IV); Fredrickson For the treatment of patients with primary dysbetalipoproteinemia ( Type III) who do not respond adequately to diet; Fredrickson To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable; As an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C remains ≥ 190 mg/dL or LDL-C remains ≥ 160 mg/dL and: there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the pediatric patient. Launch Date 1996
Hyperlipidemia 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020702s065lbl.pdf	Primary		Approved 8429	LIPITOR Approved Use Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with CHD or multiple risk factors for CHD, atorvastatin calcium tablets can be started simultaneously with diet. Atorvastatin calcium tablets are an inhibitor of HMG-CoA reductase (statin) indicated as an adjunct therapy to diet to: Reduce the risk of MI, stroke, revascularization procedures, and angina in patients without CHD, but with multiple risk factors (1.1). Reduce the risk of MI and stroke in patients with type 2 diabetes without CHD, but with multiple risk factors (1.1). Reduce the risk of non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for CHF, and angina in patients with CHD (1.1). Reduce elevated total-C, LDL-C, apo B, and TG levels and increase HDL-C in adult patients with primary hyperlipidemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (1.2). Reduce elevated TG in patients with hypertriglyceridemia and primary dysbetalipoproteinemia (1.2). Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH) (1.2). Reduce elevated total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.2). Limitations of Use Atorvastatin calcium tablets have not been studied in Fredrickson Types I and V dyslipidemias. 1.1 Prevention of Cardiovascular Disease In adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, low HDL-C, or a family history of early coronary heart disease, atorvastatin calcium tablets are indicated to: Reduce the risk of myocardial infarction Reduce the risk of stroke Reduce the risk for revascularization procedures and angina In patients with type 2 diabetes, and without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as retinopathy, albuminuria, smoking, or hypertension, atorvastatin calcium tablets are indicated to: Reduce the risk of myocardial infarction Reduce the risk of stroke In patients with clinically evident coronary heart disease, atorvastatin calcium tablets are indicated to: Reduce the risk of non-fatal myocardial infarction Reduce the risk of fatal and non-fatal stroke Reduce the risk for revascularization procedures Reduce the risk of hospitalization for CHF Reduce the risk of angina 1.2 Hyperlipidemia Atorvastatin calcium tablets are indicated: As an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia ( Types IIa and IIb); Fredrickson As an adjunct to diet for the treatment of patients with elevated serum TG levels ( Type IV); Fredrickson For the treatment of patients with primary dysbetalipoproteinemia ( Type III) who do not respond adequately to diet; Fredrickson To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable; As an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if after an adequate trial of diet therapy the following findings are present: LDL-C remains ≥ 190 mg/dL or LDL-C remains ≥ 160 mg/dL and: there is a positive family history of premature cardiovascular disease or two or more other CVD risk factors are present in the pediatric patient. Launch Date 1996

C_max

Value	Dose	Analyte	Population
8.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29683561	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ATORVASTATIN blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
9.52 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31450089	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ATORVASTATIN blood	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
33.24 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00844376	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	ATORVASTATIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
45 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29683561	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ATORVASTATIN blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
35.04 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31450089	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ATORVASTATIN blood	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
140.79 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00844376	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	ATORVASTATIN plasma	Homo sapiens
137.49 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00844376	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	ATORVASTATIN plasma	Homo sapiens
142.86 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00844376	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	ATORVASTATIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
6.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29683561	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ATORVASTATIN blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
16.57 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/31450089	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	ATORVASTATIN blood	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
7.21 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00844376	80 mg single, oral dose: 80 mg route of administration: oral experiment type: single co-administered:	ATORVASTATIN plasma	Homo sapiens

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:39548	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:39548
ChemicalBook	CB4239912	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4239912
ChemicalBook	CB81269853	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB81269853
MolPort	MolPort-000-883-773	https://www.molport.com/shop/molecule-link/MolPort-000-883-773
ZINC	ZINC000003920719	http://zinc15.docking.org/substances/ZINC000003920719
eMolecules	877278	https://www.emolecules.com/cgi-bin/more?vid=877278

PubMed

Title	Date	PubMed
Atorvastatin and simvastatin have distinct effects on hydroxy methylglutaryl-CoA reductase activity and mRNA abundance in the guinea pig.	1999 Dec	10652993
Therapeutic change of HMG-CoA reductase inhibitors in patients with coronary artery disease.	2001 Apr	11310513
Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate.	2001 Apr	11288040
Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.	2001 Apr 17	11306519
Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling.	2001 Aug	11457792
Do HMG-CoA reductase inhibitors affect fibrinogen?	2001 Feb	11215845
Drug therapy or coronary angioplasty for the treatment of coronary artery disease: new insights.	2001 Feb	11174355
A four-column parallel chromatography system for isocratic or gradient LC/MS analyses.	2001 Feb 1	11217766
Celecoxib-induced cholestatic hepatitis.	2001 Feb 6	11177350
[Lymphocyte infiltration in superficial dermis].	2001 Jan	11226907
Hypolipidemic effect of NK-104 and other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in guinea pigs.	2001 Jan	11215324
Efficacy and drug interactions of the new HMG-CoA reductase inhibitors cerivastatin and atorvastatin in CsA-treated renal transplant recipients.	2001 Jan	11209008
Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.	2001 Jan	11204586
Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin.	2001 Jan	11197581
Statins in children: what do we know and what do we need to do?	2001 Jan	11123845
New statins and new doses of older statins.	2001 Jan	11123843
Statin trials in progress: unanswered questions.	2001 Jan	11123842
Effective use of statins to prevent coronary heart disease.	2001 Jan 15	11201696
[Disturbances in cholesterol metabolism].	2001 Jan 19	11205483
[The role of HDL in the prevention of cardiovascular events].	2001 Jan 21	11217160
The effects of converting from simvastatin to atorvastatin on plasminogen activator inhibitor type-1.	2001 Jul	11452711
Statin-stimulated nitric oxide release from endothelium.	2001 Jul-Aug	11433186
HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species.	2001 Jun	11408394
Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.	2001 Jun	11403364
Effect of atorvastatin on plasminogen activator inhibitor type-1 synthesis in human monocytes/macrophages.	2001 Jun	11392473
Growth hormone reduces plasma cholesterol in LDL receptor-deficient mice.	2001 Jun	11387232
Efficacy of atorvastatin in achieving National Cholesterol Education Program low-density lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH).	2001 Jun	11376309
Limitation of heart growth in neonatal piglets by simvastatin and atorvastatin: comparison with pravastatin.	2001 Jun	11356632
Atorvastatin-induced dermatomyositis.	2001 Jun 1	11388341
Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease.	2001 Jun 19	11413075
Statin therapy--what now?	2001 Mar	11284361
HMG-CoA reductase inhibitors and P-glycoprotein modulation.	2001 Mar	11250868
F 12511, a novel ACAT inhibitor, and atorvastatin regulate endogenous hypercholesterolemia in a synergistic manner in New Zealand rabbits fed a casein-enriched diet.	2001 Mar	11223434
A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro.	2001 Mar	11181496
Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study.	2001 Mar-Apr	11428488
Statin induced myopathy does not show up in MIBI scintigraphy.	2001 May	11388581
Aggressive versus moderate lipid-lowering therapy in postmenopausal women with hypercholesterolemia: Rationale and design of the Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES) trial.	2001 May	11320358
Repeated analysis of semen parameters in beagle dogs during a 2-year study with the HMG-CoA reductase inhibitor, atorvastatin.	2001 May	11294983
Genetic analysis of digestive physiology using fluorescent phospholipid reporters.	2001 May 18	11359013

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose of atorvastatin calcium (LIPITOR®) is 10 or 20 mg once daily. Patients who require a large reduction in LDL(low-density lipoprotein)-cholesterol (more than 45%) may be started at 40 mg once daily. The dosage range of atorvastatin calcium is 10 to 80 mg once daily. Atorvastatin calcium can be administered as a single dose at any time of the day, with or without food. The starting dose and maintenance doses of atorvastatin calcium should be individualized according to patient characteristics such as goal of therapy and response. After initiation and/or upon titration of atorvastatinc calcium, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly.

Route of Administration: Oral

In Vitro Use Guide

In vitro, atorvastatin (CI-981) was equipotent as HMG-CoA reductase inhibitor in rat liver, spleen, testis and adrenal tissue (IC50 38.7 nM, 29.5 nM, 36.4, and 100.4 nM, respectively).

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:37:25 GMT 2023` Edited by `admin` on `Sat Dec 16 17:37:25 GMT 2023`
Record UNII	A0JWA85V8F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ATORVASTATIN

Official Name

English

ATORVASTATIN [HSDB]

Common Name

English

(.BETA.R,.DELTA.R)-2-(P-FLUOROPHENYL)-.BETA.,.DELTA.-DIHYDROXY-5-ISOPROPYL-3-PHENYL-4-(PHENYLCARBAMOYL)PYRROLE-1-HEPTANOIC ACID

Common Name

English

1H-PYRROLE-1-HEPTANOIC ACID, 2-(4-FLUOROPHENYL)-.BETA.,.DELTA.-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-((PHENYLAMINO)CARBONYL)-, (R-(R*,R*))-

Common Name

English

ATORVASTATIN [MI]

Common Name

English

atorvastatin [INN]

Common Name

English

Atorvastatin [WHO-DD]

Common Name

English

ATORVASTATIN [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC10BX03