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	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	410.458
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 41 Target ID: CHEMBL402 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021192s019lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10965989	Inhibitor 8146		28.0 nM [IC50]
Oligopeptide transporter small intestine isoform 6 Target ID: CHEMBL4605 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15846457	Inhibitor 8146		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 8307	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 8307	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 8307	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 1670 inhibitor 1532	substrate 985 inhibitor 1695	substrate 1168 inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2C19 1410 CYP3A 208 CYP2C8 869 P-gp 1401 BCRP 678 OAT3 625 OAT1 584	CYP1A2 1013 CYP2A6 510 CYP2B6 648 CYP2C19 955 CYP2E1 633 CYP3A5 383 CYP1A1 344 CYP2C8 670 P-gp 1491 BCRP 545 OATP1B1 389 OATP2B1 103 OATP1B3 333	CYP1A1 103

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/8737761/ Page: 3.0	moderate [IC50 100 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 1484	inhibitor 3185 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A 291	inhibitor 3185 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/17064205/	not significant
CYP3A4 1857	inhibitor 3185 Sources: https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2044.2005.04110.x	weak [Ki 94.3 uM]
CYP2C8 923	inhibitor 3185 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [IC50 20 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 26.3 uM]
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/14729100/	yes [IC50 5.79 uM]
CYP2C9 1747	inhibitor 3185 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	yes [Ki 0.3 uM]
BCRP 751	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/15955871/ Page: 5.0	yes [Ki 5.43 uM]
CYP1A1 206	inducer 1515 Sources: https://pubmed.ncbi.nlm.nih.gov/8937853/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 985	substrate 3264 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 344	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2C8 670	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP2D6 1168	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	minor
CYP3A4 1670	substrate 3264 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 1013	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2A6 510	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2B6 648	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2C19 955	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP2E1 633	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
CYP3A5 383	substrate 3264 Sources: https://dmd.aspetjournals.org/content/27/3/410.abstract	no
P-gp 1491	substrate 3264 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 333	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP2B1 103	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/17470528/	yes
OATP1B1 389	substrate 3264 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 545	substrate 3264 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
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
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
Does vitamin E beneficially affect muscle pains during HMG-Co-enzyme-A-reductase inhibitors without CK-elevation?	2000 Mar	10799017
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.	2001 Mar 8	11256847
Structural mechanism for statin inhibition of HMG-CoA reductase.	2001 May 11	11349148
Regional intestinal absorption and biliary excretion of fluvastatin in the rat: possible involvement of mrp2.	2004 Sep-Oct	16026004
Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin.	2005	16696316
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
Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat.	2008 May 31	18384769
Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice.	2009 Jan 15	19147586
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

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 `Sat Dec 17 18:04:57 UTC 2022` Edited by `admin` on `Sat Dec 17 18:04:57 UTC 2022`
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