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
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
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 |
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
Sources: http://adisinsight.springer.com/drugs/800000409
Curator's Comment: # Novartis
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL402 |
28.0 nM [IC50] | ||
Target ID: CHEMBL4605 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15846457 |
337.0 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | LESCOL Approved UseLESCOL/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 Date1993 |
|||
Primary | LESCOL Approved UseLESCOL/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 Date1993 |
|||
Primary | LESCOL Approved UseLESCOL/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 Date1993 |
Cmax
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 |
T1/2
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: 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: Page: p.505 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/8737761/ Page: 3.0 |
moderate [IC50 100 uM] | |||
no | ||||
no | ||||
no | ||||
not significant | ||||
weak [Ki 94.3 uM] | ||||
yes [IC50 20 uM] | ||||
yes [IC50 26.3 uM] | ||||
yes [IC50 5.79 uM] | ||||
yes [Ki 0.3 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/15955871/ Page: 5.0 |
yes [Ki 5.43 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/8937853/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
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%. |
|||
minor | ||||
minor | ||||
minor | ||||
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 |
|||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
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 |
||
yes | ||||
yes | ||||
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/ |
|||
yes | yes (pharmacogenomic study) Comment: AUC of drug increased by 72% |
PubMed
Title | Date | PubMed |
---|---|---|
Currently available hypolipidaemic drugs and future therapeutic developments. | 1995 Oct |
|
Effect of fluvastatin or bezafibrate on the distribution of high density lipoprotein subpopulations in patients with familial hypercholesterolemia. | 1996 Sep |
|
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 |
|
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. | 2002 Jan 11 |
|
Statins and risk of polyneuropathy: a case-control study. | 2002 May 14 |
|
Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro. | 2005 Aug |
|
Prediction of CYP2C9-mediated drug-drug interactions: a comparison using data from recombinant enzymes and human hepatocytes. | 2005 Nov |
|
Fluvastatin ameliorates podocyte injury in proteinuric rats via modulation of excessive Rho signaling. | 2006 Mar |
|
Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. | 2007 Mar |
|
Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes. | 2009 Nov |
|
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. | 2010 Dec |
|
A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women. | 2010 Mar |
|
Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter. | 2013 Jul |
|
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
|
Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy. | 2016 Jan-Feb |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/fluvastatin.html
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11273020
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
Edited
Sat Dec 16 05:15:17 GMT 2023
by
admin
on
Sat Dec 16 05:15:17 GMT 2023
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Record UNII |
PYF7O1FV7F
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C1655
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SUB02243MIG
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m5515
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BB-10
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38561
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CHEMBL2220442
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BASIS OF STRENGTH->SUBSTANCE |
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PARENT -> SALT/SOLVATE | |||
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BASIS OF STRENGTH->SUBSTANCE |
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IMPURITY -> PARENT |
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