Details
Stereochemistry | RACEMIC |
Molecular Formula | C24H26FNO4 |
Molecular Weight | 411.4659 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
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=FJLGEFLZQAZZCD-JUFISIKESA-N
InChI=1S/C24H26FNO4/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)/b12-11+/t18-,19-/m0/s1
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 |
---|---|---|
Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids. | 1991 Oct |
|
Effect of fluvastatin or bezafibrate on the distribution of high density lipoprotein subpopulations in patients with familial hypercholesterolemia. | 1996 Sep |
|
The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers. | 1999 Apr |
|
Statins and peripheral neuropathy. | 1999 Jan |
|
Search of antimicrobial activity of selected non-antibiotic drugs. | 2002 Nov-Dec |
|
In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors. | 2005 Apr |
|
Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro. | 2005 Aug |
|
Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. | 2005 Oct |
|
Chiral evaluation of fluvastatin in human plasma by high-performance liquid chromatography electrospray mass spectrometry. | 2006 Mar 7 |
|
Cardioprotective effect of fluvastatin on isoproterenol-induced myocardial infarction in rat. | 2008 May 31 |
|
In vitro interactions between primycin and different statins in their effects against some clinically important fungi. | 2010 Feb |
|
Effect of an antimicrobial agent on atherosclerotic plaques: assessment of metalloproteinase activity by molecular imaging. | 2010 Mar 23 |
|
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking. | 2012 Dec |
|
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
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.
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Classification Tree | Code System | Code | ||
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WHO-VATC |
QC10AA04
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NDF-RT |
N0000175589
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LIVERTOX |
NBK548435
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NDF-RT |
N0000000121
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NCI_THESAURUS |
C1655
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WHO-ATC |
C10AA04
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4L066368AS
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1548972
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38561
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C61768
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41127
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CHEMBL2220442
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4L066368AS
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2951
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C065180
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DB01095
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DTXSID2020636
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93957-54-1
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Fluvastatin
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100000092352
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m5515
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FLUVASTATIN
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1229
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)