FLUVASTATIN SODIUM

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H25FNO4.Na
Molecular Weight	433.4478
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CC(C)N1C(\C=C\[C@H](O)C[C@H](O)CC([O-])=O)=C(C2=C1C=CC=C2)C3=CC=C(F)C=C3

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	C24H25FNO4
Molecular Weight	410.458
Charge	-1
Count

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

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

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 46 Target ID: CHEMBL402 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10965989	Inhibitor 8228		28.0 nM [IC50]
Oligopeptide transporter small intestine isoform 6 Target ID: CHEMBL4605 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15846457	Inhibitor 8228		337.0 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypercholesterolemia 47 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8360	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 74 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8360	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 30 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf	Primary	Approved 8360	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 1709 inhibitor 1579	substrate 1010 inhibitor 1752	substrate 1193 inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2C19 1463 CYP3A 211 CYP2C8 901 P-gp 1437 BCRP 691 OAT3 636 OAT1 595	CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C19 985 CYP2E1 648 CYP3A5 391 CYP1A1 348 CYP2C8 688 P-gp 1527 BCRP 555 OATP1B1 403 OATP2B1 103 OATP1B3 347	CYP1A1 109

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/8737761/ Page: 3.0	moderate [IC50 100 uM]
CYP1A2 1673	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 1537	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A 295	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/17064205/	not significant
CYP3A4 1909	inhibitor 3240 Sources: https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2005.04110.x	weak [Ki 94.3 uM]
CYP2C8 955	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [IC50 20 uM]
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 26.3 uM]
OAT3 638	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 5.79 uM]
CYP2C9 1803	inhibitor 3240 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [Ki 0.3 uM]
BCRP 765	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/15955871/ Page: 5.0	yes [Ki 5.43 uM]
CYP1A1 218	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/8937853/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 1010	substrate 3326 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 348	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2C8 688	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2D6 1193	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP3A4 1709	substrate 3326 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 1032	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2A6 523	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2B6 660	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 985	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2E1 648	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A5 391	substrate 3326 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1527	substrate 3326 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 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP2B1 103	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP1B1 403	substrate 3326 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 555	substrate 3326 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
Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids.	1991 Oct	1656041
Fluvastatin in combination with other lipid-lowering agents.	1994 Dec	19496270
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
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
Effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on nitric oxide-induced hydroxyl radical generation in the rat heart.	2001 Apr 30	11335104
Structural mechanism for statin inhibition of HMG-CoA reductase.	2001 May 11	11349148
Statins and risk of polyneuropathy: a case-control study.	2002 May 14	12011277
Search of antimicrobial activity of selected non-antibiotic drugs.	2002 Nov-Dec	12669766
Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin.	2003 Jun	12773150
In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors.	2005 Apr	15846457
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
Binding thermodynamics of statins to HMG-CoA reductase.	2005 Sep 6	16128575
Muscle symptoms associated with statins: a series of twenty patients.	2006 Jan	16433891
Chiral evaluation of fluvastatin in human plasma by high-performance liquid chromatography electrospray mass spectrometry.	2006 Mar 7	16480934
Enantioselectivity in the pharmacokinetic interaction between fluvastatin and lercanidipine in healthy volunteers.	2009 Feb	19033449
Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice.	2009 Jan 15	19147586
In vitro interactions between primycin and different statins in their effects against some clinically important fungi.	2010 Feb	19875509
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women.	2010 Mar	19773416
Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial.	2010 Nov	20671225
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
Statin-induced inhibition of breast cancer proliferation and invasion involves attenuation of iron transport: intermediacy of nitric oxide and antioxidant defence mechanisms.	2014 Aug	24964743
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 `Thu Jul 06 11:01:55 UTC 2023` Edited by `admin` on `Thu Jul 06 11:01:55 UTC 2023`
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 [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 IMPURITY]

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 [WHO-DD]

Common Name

English

FLUVASTATIN SODIUM [USAN]

Common Name

English

ALMASTATIN

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1655