FLUVASTATIN SODIUM

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H25FNO4.Na
Molecular Weight	433.4487
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)n1c2ccccc2c(-c3ccc(cc3)F)c1/C(/[H])=C(\[H])/[C@@]([H])(C[C@@]([H])(CC(=O)[O-])O)O.[Na+]

InChI

InChIKey=ZGGHKIMDNBDHJB-RPQBTBOMSA-M

InChI=1S/C24H26FNO4.Na/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30;/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30);/q;+1/p-1/b12-11+;/t18-,19-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	Na
Molecular Weight	22.9898
Charge	1
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C24H25FNO4
Molecular Weight	410.4589
Charge	-1
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf | https://www.drugbank.ca/drugs/DB01095

Fluvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. Fluvastatin is marketed under the trade names Lescol, Canef, Vastin. LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD Slow the progression of atherosclerosis in patients with CHD. Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 39 Target ID: CHEMBL402 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10965989	Inhibitor 7728		28.0 nM [IC50]
Oligopeptide transporter small intestine isoform 5 Target ID: CHEMBL4605 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15846457	Inhibitor 7728		337.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypercholesterolemia 46 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8043	LESCOL Approved Use LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2) Launch Date 7.5729601E11
Atherosclerosis 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8043	LESCOL Approved Use LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2) Launch Date 7.5729601E11
Dyslipidemia 28 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8043	LESCOL Approved Use LESCOL/LESCOL XL is an HMG-CoA reductase inhibitor (statin) indicated as an adjunctive therapy to diet to: Reduce elevated TC, LDL-C, Apo B, and TG, and to increase HDL-C in adult patients with primary hypercholesterolemia and mixed dyslipidemia (1.1) Reduce elevated TC, LDL-C, and Apo B levels in boys and post-menarchal girls, 10 to 16 years of age, with heterozygous familial hypercholesterolemia after failing an adequate trial of diet therapy (1.1) Reduce the risk of undergoing revascularization procedures in patients with clinically evident CHD (1.2) Slow the progression of atherosclerosis in patients with CHD (1.2) Launch Date 7.5729601E11

C_max

Value	Dose	Co-administered	Analyte	Population
205 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29368187	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
206.2 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29368187	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.54 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29368187	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		FLUVASTATIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
640 mg 1 times / day multiple, oral Highest studied dose Dose: 640 mg, 1 times / day Route: oral Route: multiple Dose: 640 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11336101 Page: p.505	unhealthy, ADULT n = 7 Health Status: unhealthy Condition: lipid metabolism disorder Age Group: ADULT Sex: M+F Food Status: FED Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/11336101 Page: p.505	Sources: https://pubmed.ncbi.nlm.nih.gov/11336101 Page: p.505

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1601 inhibitor 1467	substrate 936 inhibitor 1604	substrate 1118 inhibitor 1702

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1383 CYP2C19 1325 CYP3A 191 CYP2C8 818 P-gp 1330 BCRP 643 OAT3 588 OAT1 554	CYP1A2 972 CYP2A6 485 CYP2B6 616 CYP2C19 910 CYP2E1 606 CYP3A5 367 CYP1A1 325 CYP2C8 634 P-gp 1400 BCRP 515 OATP1B1 370 OATP2B1 101 OATP1B3 319	CYP1A1 98

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1738	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/8737761/ Page: 3.0	moderate [IC50 100 uM]
CYP1A2 1532	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 1392	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A 271	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1514	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/17064205/	not significant
CYP3A4 1772	inhibitor 3045 Sources: https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2005.04110.x	weak [Ki 94.3 uM]
CYP2C8 865	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [IC50 20 uM]
OAT1 558	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 26.3 uM]
OAT3 590	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 5.79 uM]
CYP2C9 1648	inhibitor 3045 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [Ki 0.3 uM]
BCRP 713	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/15955871/ Page: 5.0	yes [Ki 5.43 uM]
CYP1A1 192	inducer 1440 Sources: https://pubmed.ncbi.nlm.nih.gov/8937853/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 936	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	major	yes (co-administration study) Comment: Coadministration with rifampicin (CYP2C9 inducer) increased the CL/F of fluvastatin by 95% and to reduce AUC by 50%. Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract
CYP1A1 325	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2C8 634	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2D6 1118	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP3A4 1601	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract; https://pubmed.ncbi.nlm.nih.gov/17064205/	minor	unknown (co-administration study) Comment: Coadministration with cyclocporine resulted in 3.1-fold increase in AUC; however, cannot be explained through these mechanisms, since neither pravastatin nor fluvastatin has been shown to be a substrate for either P-gp or CYP3A4; coadministration with itraconazole had no significant impact on Cmax and AUC of fluvastatin Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract; https://pubmed.ncbi.nlm.nih.gov/17064205/
CYP1A2 972	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2A6 485	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2B6 616	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 910	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2E1 606	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A5 367	substrate 3113 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1400	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/11368292/ Page: 14.0	no	unknown (co-administration study) Comment: Coadministration with cyclocporine resulted in 3.1-fold increase in AUC; however, cannot be explained through these mechanisms, since neither pravastatin nor fluvastatin has been shown to be a substrate for either P-gp or CYP3A4 Sources: https://pubmed.ncbi.nlm.nih.gov/11368292/ Page: 14.0
OATP1B3 319	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP2B1 101	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP1B1 370	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes	unlikely (co-administration study) Comment: coadministered with rifampin. See https://pubmed.ncbi.nlm.nih.gov/29768081/. Pharmacogenomic study also performed. Not significant: see https://www.lipidjournal.com/article/S1933-2874(14)00072-5/pdf Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/
BCRP 515	substrate 3113 Sources: https://www.jpharmsci.org/article/S0022-3549(16)30083-1/pdf	yes	yes (pharmacogenomic study) Comment: AUC of drug increased by 72% Sources: https://www.jpharmsci.org/article/S0022-3549(16)30083-1/pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:38561	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:38561
ChemicalBook	CB03386396	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB03386396
MolPort	MolPort-006-167-704	https://www.molport.com/shop/molecule-link/MolPort-006-167-704
ZINC	ZINC000001530639	http://zinc15.docking.org/substances/ZINC000001530639
eMolecules	10141252	https://www.emolecules.com/cgi-bin/more?vid=10141252

PubMed

Title	Date	PubMed
Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.	1994 Jun 6	8017468
Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin-cholestyramine combination.	1994 May	8192170
Currently available hypolipidaemic drugs and future therapeutic developments.	1995 Oct	8593127
Fluvastatin in combination with other lipid-lowering agents.	1996 Jan	8729588
Effect of fluvastatin or bezafibrate on the distribution of high density lipoprotein subpopulations in patients with familial hypercholesterolemia.	1996 Sep	8876936
A head-to-head comparison of the cost effectiveness of HMG-CoA reductase inhibitors and fibrates in different types of primary hyperlipidemia.	1997 Jan	9110123
Troglitazone upregulates LDL receptor activity in HepG2 cells.	1998 Aug	9703316
Postural hypotension induced by paroxetine.	1998 Feb 21	9518913
[Cardiology in 1997].	1998 Oct 5	9818470
Statins and peripheral neuropathy.	1999 Jan	10027656
Statin + fibrate combination therapy fluvastatin with bezafibrate or ciprofibrate in high risk patients with vascular disease.	1999 Jun 1	10402106
Enhancement of low density lipoprotein catabolism by non-steroidal anti-inflammatory drugs in cultured HepG2 cells.	1999 May 21	10395027
Effects of fluvastatin and bezafibrate combination on plasma fibrinogen, t-plasminogen activator inhibitor and C reactive protein levels in coronary artery disease patients with mixed hyperlipidaemia (FACT study). Fluvastatin Alone and in Combination Treatment.	2000 Apr	10780315
Structural mechanism for statin inhibition of HMG-CoA reductase.	2001 May 11	11349148
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002 Jan 11	11779144
Effect of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins) on tissue paraoxonase 1 and plasma platelet activating factor acetylhydrolase activities.	2004 Jan	14668577
Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin.	2005	16696316
Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro.	2005 Aug	16029222
Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin.	2005 Aug	15901796
[Fluvastatin-induced dermatomyositis].	2005 Dec	16446645
Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor.	2005 Jul	15802384
Immediate effects of fluvastain on circulating soluble endothelial protein C and free tissue factor pathway inhibitor in acute coronary syndromes.	2005 May	16142594
Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes.	2005 Nov	16081671
Focal seizures after treatment with fluvastatin in a patient with a history of catastrophic antiphospholipid syndrome.	2005 Nov 15	16111706
Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells.	2005 Oct	16046661
Evaluation of the anti-HIV activity of statins.	2005 Oct 14	16184043
Binding thermodynamics of statins to HMG-CoA reductase.	2005 Sep 6	16128575
Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study.	2006 Dec	17031388
Muscle symptoms associated with statins: a series of twenty patients.	2006 Jan	16433891
Effect of low-density lipoprotein cholesterol on angiotensin II sensitivity: a randomized trial with fluvastatin.	2006 Jun	16618834
Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma.	2007 Mar	16996129
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.	2010 Dec	20829430
Effect of an antimicrobial agent on atherosclerotic plaques: assessment of metalloproteinase activity by molecular imaging.	2010 Mar 23	20298932
Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial.	2010 Nov	20671225
The phototoxicity of fluvastatin, an HMG-CoA reductase inhibitor, is mediated by the formation of a benzocarbazole-like photoproduct.	2010 Nov	20668001
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.	2012 Dec	22733274
Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter.	2013 Jul	23564645
ATP-dependent transport of statins by human and rat MRP2/Mrp2.	2013 Jun 1	23562342
Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes.	2014 Sep	24909372
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541
Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.	2016 Jan-Feb	24451297

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Hyperlipidemia Immediate Release Capsules: -Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day -LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day -Maintenance dose: 20 mg to 80 mg per day Usual Adult Dose for Hyperlipoproteinemia Type IIa (Elevated LDL) Immediate Release Capsules: -Low-density lipoprotein cholesterol (LDL-C) reduction to a goal of 25% or greater: Initial dose of 40 mg orally once a day in the evening or 40 mg orally twice a day -LDL-C reduction to a goal of less than 25%: Initial dose of 20 mg orally once a day -Maintenance dose: 20 mg to 80 mg per day

Route of Administration: Oral

In Vitro Use Guide

Fluvastatin markedly inhibits the formation of thiobarbituric acid reactive substances in iron (II)-supported peroxidation of liposomes with IC50 of 12 uM. Fluvastatin ranging from 1 uM to 100 uM inhibits peroxyl radical-mediated peroxidation of liposomes induced by water-soluble and lipid-soluble radical generators, 2,2'-azobis (2-amidinopropane) dihydro-chloride and 2,2'-azobis (2,4-dimethylvaleronitrile), respectively.

Substance Class	Chemical Created by `admin` on `Fri Jun 25 20:59:55 UTC 2021` Edited by `admin` on `Fri Jun 25 20:59:55 UTC 2021`
Record UNII	PYF7O1FV7F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLUVASTATIN SODIUM

Official Name

English

6-HEPTENOIC ACID, 7-(3-(4-FLUOROPHENYL)-1-(1-METHYLETHYL)-1H-INDOL-2-YL)-3,5-DIHYDROXY-, MONOSODIUM SALT, (R*,S*-(E))-(+/-)-

Common Name

English

LIPAXAN

Brand Name

English

FRACTAL

Brand Name

English

FLUVASTATIN SODIUM SALT [MI]

Common Name

English

CANEF

Brand Name

English

LESCOL

Brand Name

English

SODIUM (+/-)-(3R*,5S*,6E)-7-(3-(P-FLUOROPHENYL)-1-ISOPROPYLINDOL-2-YL)-3,5-DIHYDROXY-6-HEPTENOATE

Common Name

English

FLUINDOSTATIN

Common Name

English

VASTIN

Brand Name

English

LOCOL

Brand Name

English

XU 62-320

Code

English

CRANOC

Brand Name

English

XU-62-320

Code

English

FLUVASTATIN SODIUM [ORANGE BOOK]

Common Name

English

FLUVASTATIN SODIUM [WHO-DD]

Common Name

English

FLUVASTATIN SODIUM [MART.]

Common Name

English

FLUVASTATIN SODIUM [USP MONOGRAPH]

Common Name

English

LOCHOL

Brand Name

English

FLUVASTATIN SODIUM [JAN]

Common Name

English

FLUVASTATIN SODIUM [EP MONOGRAPH]

Common Name

English

FLUVASTATIN SODIUM [USP-RS]

Common Name

English

PRIMEXIN

Brand Name

English

FLUVASTATIN SODIUM SALT

Common Name

English

FLUVASTATIN SODIUM [VANDF]

Common Name

English

FLUVASTATIN SODIUM [USP]

Common Name

English

FLUVASTATIN SODIUM [USAN]

Common Name

English

ALMASTATIN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1655