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
Synthetic statins: more data on newer lipid-lowering agents.	2001	11464449
Atorvastatin prevents glomerulosclerosis and renal endothelial dysfunction in hypercholesterolaemic rabbits.	2001	11369819
Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia.	2001	11304935
Effects of statins on biomarkers of bone metabolism: a randomised trial.	2001 Apr	11434192
The efficacy of atorvastatin in treating patients with hypercholesterolaemia to target LDL-cholesterol goals: the LIPI-GOAL trial.	2001 Apr	11357922
Therapeutic change of HMG-CoA reductase inhibitors in patients with coronary artery disease.	2001 Apr	11310513
Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use of reductase inhibitors for intracranial plaque stabilization.	2001 Apr	11296593
Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate.	2001 Apr	11288040
Tachyphylaxis in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.	2001 Apr 15	11327075
Assessing the results: phase 1 hyperlipidemia outcomes in 27 health plans.	2001 Apr 16	11311193
Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.	2001 Apr 17	11306519
Lipid-lowering therapy in acute coronary syndromes.	2001 Apr 4	11277832
Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.	2001 Apr 4	11277825
[Prevention in coronary heart disease. Can a CSE inhibitor arrest calcium deposits?].	2001 Apr 5	11340911
Effect of atorvastatin on low-density lipoprotein subtypes in patients with different forms of hyperlipoproteinemia and control subjects.	2001 Aug	11474489
The effect of aggressive versus standard lipid lowering by atorvastatin on diabetic dyslipidemia: the DALI study: a double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes and diabetic dyslipidemia.	2001 Aug	11473066
Heart rate variability after long-term treatment with atorvastatin in hypercholesterolaemic patients with or without coronary artery disease.	2001 Aug	11472748
Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling.	2001 Aug	11457792
Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.	2001 Aug 1	11472706
Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B: effect of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on non-high-density lipoprotein cholesterol levels.	2001 Aug 1	11472705
Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia.	2001 Feb	11383326
Treatment of heterozygous familial hypercholesterolemia: atorvastatin vs simvastatin.	2001 Feb	11383320
Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease.	2001 Feb	11293560
Elevated baseline triglyceride levels modulate effects of HMGCoA reductase inhibitors on plasma lipoproteins.	2001 Jan	11452336
Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells.	2001 Jul	11427209
Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease.	2001 Jul 24	11468198
Statin-stimulated nitric oxide release from endothelium.	2001 Jul-Aug	11433186
HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein.	2001 Jun	11474784
The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3.	2001 Jun	11471927
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
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
[Atorvastatin].	2001 Mar	11347138
[AVERT [The Atorvastatin versus Revascularization Treatment]].	2001 Mar	11347110
Statin therapy--what now?	2001 Mar	11284361
[Decreasing blood lipids for prevention of coronary heart disease--discussion of the "permissive LDL level". Diagnostic imaging facilitates therapeutic decision].	2001 Mar 29	11332020
Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study.	2001 Mar-Apr	11428488
Dermographism: an adverse effect of atorvastatin.	2001 Mar-Apr	11314923
A cost-effectiveness model of alternative statins to achieve target LDL-cholesterol levels.	2001 May	11406909
Statin induced myopathy does not show up in MIBI scintigraphy.	2001 May	11388581
Atorvastatin.	2001 May	11336625
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
Structural mechanism for statin inhibition of HMG-CoA reductase.	2001 May 11	11349148
Genetic analysis of digestive physiology using fluorescent phospholipid reporters.	2001 May 18	11359013
Cost effectiveness of HMG-CoA reductase inhibition in Canada.	2001 Spring	11283756

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