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Details

Stereochemistry ABSOLUTE
Molecular Formula 2C33H34FN2O5.Ca
Molecular Weight 1155.342
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ATORVASTATIN CALCIUM ANHYDROUS

SMILES

[Ca++].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.CC(C)C5=C(C(=O)NC6=CC=CC=C6)C(=C(N5CC[C@@H](O)C[C@@H](O)CC([O-])=O)C7=CC=C(F)C=C7)C8=CC=CC=C8

InChI

InChIKey=FQCKMBLVYCEXJB-MNSAWQCASA-L
InChI=1S/2C33H35FN2O5.Ca/c2*1-21(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;/h2*3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40);/q;;+2/p-2/t2*26-,27-;/m11./s1

HIDE SMILES / InChI

Molecular Formula Ca
Molecular Weight 40.078
Charge 2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C33H34FN2O5
Molecular Weight 557.6319
Charge -1
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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.

Originator

Curator's Comment: In 2000 Pfizer bought Warner-Lambert along with all of its subsidiary companies.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
14.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
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

8.5078082E11
Primary
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

8.5078082E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8.8 ng/mL
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
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
80 mg single, oral
dose: 80 mg
route of administration: oral
experiment type: single
co-administered:
ATORVASTATIN plasma
Homo sapiens
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
45 ng × h/mL
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
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
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
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
80 mg single, oral
dose: 80 mg
route of administration: oral
experiment type: single
co-administered:
ATORVASTATIN plasma
Homo sapiens
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.2 h
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
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
80 mg single, oral
dose: 80 mg
route of administration: oral
experiment type: single
co-administered:
ATORVASTATIN plasma
Homo sapiens
PubMed

PubMed

TitleDatePubMed
Synthetic statins: more data on newer lipid-lowering agents.
2001
Hypertriglyceridemia: a review of clinical relevance and treatment options: focus on cerivastatin.
2001
A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial.
2001
Atorvastatin prevents glomerulosclerosis and renal endothelial dysfunction in hypercholesterolaemic rabbits.
2001
Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia.
2001
The effect of atorvastatin on serum lipids, lipoprotein(a) and plasma fibrinogen levels in primary dyslipidaemia--a pilot study involving serial sampling.
2001
Effects of statins on biomarkers of bone metabolism: a randomised trial.
2001 Apr
The efficacy of atorvastatin in treating patients with hypercholesterolaemia to target LDL-cholesterol goals: the LIPI-GOAL trial.
2001 Apr
Therapeutic change of HMG-CoA reductase inhibitors in patients with coronary artery disease.
2001 Apr
[Prevention in coronary heart disease. Can a CSE inhibitor arrest calcium deposits?].
2001 Apr 5
Effect of atorvastatin on low-density lipoprotein subtypes in patients with different forms of hyperlipoproteinemia and control subjects.
2001 Aug
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
Heart rate variability after long-term treatment with atorvastatin in hypercholesterolaemic patients with or without coronary artery disease.
2001 Aug
Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling.
2001 Aug
Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.
2001 Aug 1
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
Effects of atorvastatin and omega-3 fatty acids on LDL subfractions and postprandial hyperlipemia in patients with combined hyperlipemia.
2001 Feb
Treatment of heterozygous familial hypercholesterolemia: atorvastatin vs simvastatin.
2001 Feb
Cost-minimization analysis of simvastatin versus atorvastatin for maintenance therapy in patients with coronary or peripheral vascular disease.
2001 Feb
[Statins and unstable angina: MIRACL].
2001 Feb
[Statins and diabetic hyperlipidemia].
2001 Feb
Do HMG-CoA reductase inhibitors affect fibrinogen?
2001 Feb
Celecoxib-induced cholestatic hepatitis.
2001 Feb 6
Aggressive LDL-cholesterol lowering with atorvastatin results in regression of atherosclerosis.
2001 Feb-Mar
Elevated baseline triglyceride levels modulate effects of HMGCoA reductase inhibitors on plasma lipoproteins.
2001 Jan
[Cost-effectiveness of atorvastatin against simvastatin as hypolipemic treatment in hypercholesterolemic patients in primary care].
2001 Jan
Statin trials in progress: unanswered questions.
2001 Jan
Effective use of statins to prevent coronary heart disease.
2001 Jan 15
The effects of converting from simvastatin to atorvastatin on plasminogen activator inhibitor type-1.
2001 Jul
Cerivastatin triggers tumor-specific apoptosis with higher efficacy than lovastatin.
2001 Jul
Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells.
2001 Jul
Atorvastatin versus micronized fenofibrate in the treatment of patients with mixed hyperlipoproteinemia.
2001 Jul 15
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
Statin-stimulated nitric oxide release from endothelium.
2001 Jul-Aug
HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein.
2001 Jun
The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3.
2001 Jun
Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia.
2001 Jun
Low-density lipoprotein apheresis in a patient aged 3.5 years.
2001 Jun
Is a mechanical or a metabolic approach superior in the treatment of coronary disease? Results of the atorvastatin versus revascularization (AVERT) trial.
2001 Jun
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
Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease.
2001 Jun 19
[AVERT [The Atorvastatin versus Revascularization Treatment]].
2001 Mar
Statin therapy--what now?
2001 Mar
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
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.
2001 Mar 8
Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study.
2001 Mar-Apr
Statin induced myopathy does not show up in MIBI scintigraphy.
2001 May
Atorvastatin.
2001 May
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
Patents

Sample Use Guides

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 Thu Jul 06 00:02:47 UTC 2023
Edited
by admin
on Thu Jul 06 00:02:47 UTC 2023
Record UNII
C0GEJ5QCSO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ATORVASTATIN CALCIUM ANHYDROUS
Common Name English
1H-PYRROLE-1-HEPTANOIC ACID, 2-(4-FLUOROPHENYL)-.BETA.,.GAMMA.-DIHYDROXY-5- (1-METHYLETHYL)-3-PHENYL-4-((PHENYLAMINO)CARBONYL)-, CALCIUM SALT (2:1), (.BETA.R,.GAMMA.R)-
Common Name English
ATORVASTATIN CALCIUM (ANHYDROUS)
Common Name English
CALCIUM (.BETA.R,.DELTA.R)-2-(P-FLUOROPHENYL)-.BETA.,.DELTA.-DIHYDROXY-5-ISOPROPYL-3-PHENYL-4-(PHENYLCARBAMOYL)PYRROLE-1-HEPTANOATE (1:2)
Common Name English
1H-PYRROLE-1-HEPTANOIC ACID, 2-(4-FLUOROPHENYL)-B,D-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-((PHENYLAMINO)CARBONYL)-, CALCIUM SALT (2:1), (R-(R*,R*))-
Common Name English
Atorvastatin calcium [WHO-DD]
Common Name English
NSC-758617
Code English
ATORVASTATIN CALCIUM SALT ANHYDROUS [MI]
Common Name English
1H-PYRROLE-1-HEPTANOIC ACID, 2-(4-FLUOROPHENYL)-.BETA.,.DELTA.-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-((PHENYLAMINO)CARBONYL)-, CALCIUM SALT (2:1), (R-(R*,R*))-
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1655
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
Code System Code Type Description
FDA UNII
C0GEJ5QCSO
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
RXCUI
2569977
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
NSC
758617
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
EPA CompTox
DTXSID6044303
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
CAS
134523-03-8
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
MERCK INDEX
M2125
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
DAILYMED
C0GEJ5QCSO
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
PUBCHEM
60822
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
NCI_THESAURUS
C78759
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
SMS_ID
100000090303
Created by admin on Thu Jul 06 00:02:48 UTC 2023 , Edited by admin on Thu Jul 06 00:02:48 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
SOLVATE->ANHYDROUS
SOLVATE->ANHYDROUS
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY