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Details

Stereochemistry ABSOLUTE
Molecular Formula 2C33H34FN2O5.Sr.10H2O
Molecular Weight 1383.04
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Atorvastatin strontium pentahydrate

SMILES

O.O.O.O.O.O.O.O.O.O.[Sr++].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=BBDJXEPNNLXCKB-OIHIBBKGSA-L
InChI=1S/2C33H35FN2O5.10H2O.Sr/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);10*1H2;/q;;;;;;;;;;;;+2/p-2/t2*26-,27-;;;;;;;;;;;/m11.........../s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula Sr
Molecular Weight 87.62
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
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
Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use of reductase inhibitors for intracranial plaque stabilization.
2001 Apr
Tachyphylaxis in 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
2001 Apr 15
Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels.
2001 Apr 17
[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
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
[Statins and unstable angina: MIRACL].
2001 Feb
[Statins and diabetic hyperlipidemia].
2001 Feb
Aggressive LDL-cholesterol lowering with atorvastatin results in regression of atherosclerosis.
2001 Feb-Mar
[Atorvastatin (Lipitor): a review of its pharmacological and clinical profile].
2001 Jan
The effects of converting from simvastatin to atorvastatin on plasminogen activator inhibitor type-1.
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
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
Low-density lipoprotein apheresis in a patient aged 3.5 years.
2001 Jun
HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species.
2001 Jun
Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.
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
Limitation of heart growth in neonatal piglets by simvastatin and atorvastatin: comparison with pravastatin.
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
[Atorvastatin].
2001 Mar
[AVERT [The Atorvastatin versus Revascularization Treatment]].
2001 Mar
Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness.
2001 Mar
[Decreasing blood lipids for prevention of coronary heart disease--discussion of the "permissive LDL level". Diagnostic imaging facilitates therapeutic decision].
2001 Mar 29
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
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
Determinants of variable response to statin treatment in patients with refractory familial hypercholesterolemia.
2001 May
Repeated analysis of semen parameters in beagle dogs during a 2-year study with the HMG-CoA reductase inhibitor, atorvastatin.
2001 May
Structural mechanism for statin inhibition of HMG-CoA reductase.
2001 May 11
Genetic analysis of digestive physiology using fluorescent phospholipid reporters.
2001 May 18
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 Sat Dec 16 19:20:16 UTC 2023
Edited
by admin
on Sat Dec 16 19:20:16 UTC 2023
Record UNII
5F4N5Y2B7Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Atorvastatin strontium pentahydrate
Common Name English
Atorvastatin strontium pentahydrate [WHO-DD]
Common Name English
1H-Pyrrole-1-heptanoic acid, 2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-, strontium salt, hydrate (2:1:10), (βR,δR)-
Systematic Name English
Code System Code Type Description
PUBCHEM
164888920
Created by admin on Sat Dec 16 19:20:17 UTC 2023 , Edited by admin on Sat Dec 16 19:20:17 UTC 2023
PRIMARY
FDA UNII
5F4N5Y2B7Y
Created by admin on Sat Dec 16 19:20:17 UTC 2023 , Edited by admin on Sat Dec 16 19:20:17 UTC 2023
PRIMARY
CAS
1072903-93-5
Created by admin on Sat Dec 16 19:20:17 UTC 2023 , Edited by admin on Sat Dec 16 19:20:17 UTC 2023
PRIMARY
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ACTIVE MOIETY