Details
Stereochemistry | RACEMIC |
Molecular Formula | C24H26FNO4 |
Molecular Weight | 411.4668 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)n1c2ccccc2c(-c3ccc(cc3)F)c1/C(/[H])=C(\[H])/[C@@]([H])(C[C@@]([H])(CC(=O)O)O)O
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 Date7.5729601E11 |
|||
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 Date7.5729601E11 |
|||
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 Date7.5729601E11 |
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 |
---|---|---|
Troglitazone upregulates LDL receptor activity in HepG2 cells. | 1998 Aug |
|
Postural hypotension induced by paroxetine. | 1998 Feb 21 |
|
[Cardiology in 1997]. | 1998 Oct 5 |
|
Statin + fibrate combination therapy fluvastatin with bezafibrate or ciprofibrate in high risk patients with vascular disease. | 1999 Jun 1 |
|
Enhancement of low density lipoprotein catabolism by non-steroidal anti-inflammatory drugs in cultured HepG2 cells. | 1999 May 21 |
|
A HMG-CoA reductase inhibitor possesses a potent anti-atherosclerotic effect other than serum lipid lowering effects--the relevance of endothelial nitric oxide synthase and superoxide anion scavenging action. | 2001 Apr |
|
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 |
|
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. | 2001 Mar 8 |
|
Structural mechanism for statin inhibition of HMG-CoA reductase. | 2001 May 11 |
|
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. | 2002 Jan 11 |
|
Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin. | 2003 Jun |
|
Expression of serum and glucocorticoid-inducible kinase1 in diabetic rats and its modulation by fluvastatin. | 2005 |
|
In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors. | 2005 Apr |
|
Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. | 2005 Oct |
|
Effects of chronic treatment with statins and fenofibrate on rat skeletal muscle: a biochemical, histological and electrophysiological study. | 2006 Dec |
|
Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. | 2007 Mar |
|
Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice. | 2009 Jan 15 |
|
Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes. | 2009 Nov |
|
In vitro interactions between primycin and different statins in their effects against some clinically important fungi. | 2010 Feb |
|
Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial. | 2010 Nov |
|
Statins alter the hepatobiliary transport of unconjugated and conjugated bilirubin in sandwich-cultured rat hepatocytes. | 2014 Sep |
|
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.
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Brand Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
WHO-VATC |
QC10AA04
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
||
|
NDF-RT |
N0000175589
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
||
|
LIVERTOX |
430
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
||
|
NDF-RT |
N0000000121
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
||
|
NCI_THESAURUS |
C1655
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
||
|
WHO-ATC |
C10AA04
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
1548972
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
C61768
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
41127
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | RxNorm | ||
|
CHEMBL2220442
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
4L066368AS
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
2951
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
C065180
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
6547
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
8366
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
SUB07768MIG
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
DB01095
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
93957-54-1
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
93957-54-1
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
Fluvastatin
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
M5515
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | Merck Index | ||
|
FLUVASTATIN
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY | |||
|
1229
Created by
admin on Fri Jun 25 22:02:40 UTC 2021 , Edited by admin on Fri Jun 25 22:02:40 UTC 2021
|
PRIMARY |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)