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Details

Stereochemistry EPIMERIC
Molecular Formula 2C33H34FN2O5.C3H8O2.Ca
Molecular Weight 1231.436
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ATORVASTATIN CALCIUM PROPYLENE GLYCOL SOLVATE

SMILES

[Ca++].CC(O)CO.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=KNMXZASRMVGUNA-SVWYKLQNSA-L
InChI=1S/2C33H35FN2O5.C3H8O2.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;1-3(5)2-4;/h2*3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40);3-5H,2H2,1H3;/q;;;+2/p-2/t2*26-,27-;;/m11../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

Molecular Formula C3H6O2
Molecular Weight 74.0785
Charge -2
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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

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
Atorvastatin-induced cholestatic hepatitis in a young woman with systemic lupus erythematosus. Grupo Lupus Virgen de las Nieves.
1999 Aug 9-23
Cholesterol-lowering effect of NK-104, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in guinea pig model of hyperlipidemia.
2001
Comparative study of HMG-CoA reductase inhibitors on fibrinogen.
2001 Apr
Assessing the results: phase 1 hyperlipidemia outcomes in 27 health plans.
2001 Apr 16
[Prevention in coronary heart disease. Can a CSE inhibitor arrest calcium deposits?].
2001 Apr 5
Human breath isoprene and its relation to blood cholesterol levels: new measurements and modeling.
2001 Aug
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
Do HMG-CoA reductase inhibitors affect fibrinogen?
2001 Feb
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
Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin.
2001 Jan
Statin trials in progress: unanswered questions.
2001 Jan
Effective use of statins to prevent coronary heart disease.
2001 Jan 15
[Disturbances in cholesterol metabolism].
2001 Jan 19
[The role of HDL in the prevention of cardiovascular events].
2001 Jan 21
HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein.
2001 Jun
Low-density lipoprotein apheresis in a patient aged 3.5 years.
2001 Jun
Effect of atorvastatin on plasminogen activator inhibitor type-1 synthesis in human monocytes/macrophages.
2001 Jun
Growth hormone reduces plasma cholesterol in LDL receptor-deficient mice.
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
Atorvastatin-induced dermatomyositis.
2001 Jun 1
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
HMG-CoA reductase inhibitors and P-glycoprotein modulation.
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
Tachyphylaxis and statin drugs.
2001 Mar 1
Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study.
2001 Mar-Apr
A cost-effectiveness model of alternative statins to achieve target LDL-cholesterol levels.
2001 May
Statin induced myopathy does not show up in MIBI scintigraphy.
2001 May
Atorvastatin.
2001 May
Structural mechanism for statin inhibition of HMG-CoA reductase.
2001 May 11
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 09:32:10 UTC 2023
Edited
by admin
on Thu Jul 06 09:32:10 UTC 2023
Record UNII
YRZ789OWMI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ATORVASTATIN CALCIUM PROPYLENE GLYCOL SOLVATE
Common Name English
Atorvastatin calcium propylene glycol solvate [WHO-DD]
Common Name English
CALCIUM BIS((3R,5R)-7-(3-(ANILINOCARBONYL)-5-(4-FLUOROPHENYL)-2-ISOPROPYL-4-PHENYL-1H-PYRROL-1-YL)-3,5-DIHYDROXYHEPTANOATE) PROPYLENE GLYCOL SOLVATE
Common Name English
1H-PYRROLE-1-HEPTANOIC ACID, 2-(4-FLUOROPHENYL)-.BETA.,.DELTA.-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-((PHENYLAMINO)CARBONYL)-, CALCIUM SALT, (.BETA.R,.DELTA.R)-, COMPD. WITH 1,2-PROPANEDIOL (2:1:1)
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID10146226
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY
CAS
1040350-07-9
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY
DAILYMED
YRZ789OWMI
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY
RXCUI
1483793
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY RxNorm
PUBCHEM
51039411
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY
FDA UNII
YRZ789OWMI
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY
SMS_ID
100000142105
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY
EVMPD
SUB114506
Created by admin on Thu Jul 06 09:32:10 UTC 2023 , Edited by admin on Thu Jul 06 09:32:10 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
ANHYDROUS->SOLVATE
Related Record Type Details
ACTIVE MOIETY