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Identification
Name Fenofibrate
Accession Number DB01039 (APRD00405)
Type small molecule
Groups approved
Description

An antilipemic agent which reduces both cholesterol and triglycerides in the blood. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Fenofibrato [INN-Spanish]
  • Fenofibratum [INN-Latin]
  • Fenofibric acid
  • Finofibrate
  • FNF
Brand names
  • Ankebin
  • Antara
  • Elasterate
  • Elasterin
  • Fenobrate
  • Fenogal
  • Fenotard
  • Lipanthyl
  • Lipantil
  • Lipidex
  • Lipidil
  • Lipidil Micro
  • Lipidil Supra
  • Lipifen
  • Lipirex
  • Lipoclar
  • Lipofene
  • Liposit
  • Lipsin
  • Lofibra
  • Luxacor
  • Nolipax
  • Procetofen
  • Proctofene
  • Protolipan
  • Secalip
  • Sedufen
  • Tricor
  • Triglide
  • Trilipix (Abbott Laboratories)
Brand name mixtures Not Available
Categories
  • Antilipemic Agents
  • Fribic Acid Derivatives
CAS number 49562-28-9
Weight Average: 360.831
Monoisotopic: 360.112836867
Chemical Formula C20H21ClO4
InChI Key InChIKey=YMTINGFKWWXKFG-UHFFFAOYSA-N
InChI
InChI=1S/C20H21ClO4/c1-13(2)24-19(23)20(3,4)25-17-11-7-15(8-12-17)18(22)14-5-9-16(21)10-6-14/h5-13H,1-4H3
Plain Text
IUPAC Name
propan-2-yl 2-{4-[(4-chlorophenyl)carbonyl]phenoxy}-2-methylpropanoate
SMILES
CC(C)OC(=O)C(C)(C)OC1=CC=C(C=C1)C(=O)C1=CC=C(Cl)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzophenones
Substructures
  • Carboxylic Acids and Derivatives
  • Acetates
  • Phenols and Derivatives
  • Phenoxyacetates
  • Short-chain Hydroxy Acids
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Aromatic compounds
  • Anisoles
  • Benzophenones
  • Benzoyl Derivatives
  • Phenyl Esters
  • Ketones
Pharmacology
Indication For use as adjunctive therapy to diet to reduce elevated LDL-C, Total-C,Triglycerides and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb)
Pharmacodynamics Fenofibrate is a lipid regulating agent indicated as adjunctive therapy to diet to reduce elevated LDL-C, Total-C,Triglycerides and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb). Fenofibrate is also indicated as adjunctive therapy to diet for treatment of adult patients with hypertriglyceridemia (Fredrickson Types IV and V hyperlipidemia). Fenofibric acid, the active metabolite of Fenofibrate, produces reductions in total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in high density lipoprotein (HDL) and apoproteins apoAI and apoAII.
Mechanism of action Fenofibrate exerts its therapeutic effects through activation of peroxisome proliferator activated receptor a (PPARa). This increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III. The resulting fall in triglycerides produces an alteration in the size and composition of LDL from small, dense particles, to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly.
Absorption Fenofibrate is well absorbed from the gastrointestinal tract. After absorption, fenofibrate is mainly excreted in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide
Volume of distribution
  • 95 L [moderate renal impairment (creatinine clearance of 50 to 90 mL/min)]
  • 30 L [healthy adults]
Protein binding ~99% (Serum protein binding)
Metabolism
Route of elimination Fenofibric acid is primarily conjugated with glucuronic acid and then excreted in urine. Following oral administration in healthy volunteers, approximately 60% of a single dose of radiolabelled fenofibrate appeared in urine, primarily as fenofibric acid and its glucuronate conjugate and 25% was excreted in the feces.
Half life 20 hours
Clearance
  • 1.2 L/h [Eldery]
Toxicity LD50=1600 mg/kg (Oral, in mice); Investigated as a teratogen and reproductive hazard.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Abbott laboratories
  • Lupin atlantis holdings sa
  • Impax laboratories inc
  • Teva pharmaceuticals usa inc
  • Abbott laboratories pharmaceutical products div
  • Cipher pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Shionogi pharma inc
  • Skyepharma ag
  • Ar holding co inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Tablet Oral
Prices
Unit description Cost Unit
Triglide 160 mg tablet 6.39 USD tablet
Fenoglide 120 mg tablet 5.17 USD tablet
Antara 130 mg capsule 5.13 USD capsule
Tricor 145 mg tablet 4.69 USD tablet
Lipofen 150 mg capsule 3.55 USD capsule
Lofibra 200 mg capsule 3.25 USD capsule
Lofibra 160 mg tablet 3.11 USD tablet
Fenofibrate Micronized 200 mg capsule 2.77 USD capsule
Fenofibrate 160 mg 2.47 USD tablet
Fenofibrate 160 mg tablet 2.38 USD tablet
Lofibra 134 mg capsule 2.03 USD capsule
Antara 43 mg capsule 1.8 USD capsule
Fenofibrate Micronized 134 mg capsule 1.79 USD capsule
Fenoglide 40 mg tablet 1.72 USD tablet
Tricor 48 mg tablet 1.63 USD tablet
Triglide 50 mg tablet 1.49 USD tablet
Lipidil Supra 160 mg Tablet 1.4 USD tablet
Lofibra 67 mg capsule 1.26 USD capsule
Lipidil Micro 200 mg Capsule 1.23 USD capsule
Lipidil Supra 100 mg Tablet 1.22 USD tablet
Apo-Feno-Micro 200 mg Capsule 1.14 USD capsule
Fenofibrate Micro 200 mg Capsule 1.14 USD capsule
Mylan-Fenofibrate Micro 200 mg Capsule 1.14 USD capsule
Novo-Fenofibrate Micronized 200 mg Capsule 1.14 USD capsule
Pms-Fenofibrate Micro 200 mg Capsule 1.14 USD capsule
Ratio-Fenofibrate Mc 200 mg Capsule 1.14 USD capsule
Fenofibrate Micronized 67 mg capsule 1.0 USD capsule
Lofibra 54 mg tablet 0.99 USD tablet
Fenofibrate 54 mg tablet 0.81 USD tablet
Apo-Feno-Super 160 mg Tablet 0.79 USD tablet
Novo-Fenofibrate-S 160 mg Tablet 0.79 USD tablet
Sandoz Fenofibrate S 160 mg Tablet 0.79 USD tablet
Apo-Feno-Super 100 mg Tablet 0.68 USD tablet
Novo-Fenofibrate-S 100 mg Tablet 0.68 USD tablet
Sandoz Fenofibrate S 100 mg Tablet 0.68 USD tablet
Apo-Fenofibrate 100 mg Capsule 0.64 USD capsule
Apo-Feno-Micro 67 mg Capsule 0.45 USD capsule
Novo-Fenofibrate Micronized 67 mg Capsule 0.45 USD capsule
Patents
Country Patent Number Approved Expires
United States 7569612 2007-08-20 2027-08-20
United States 5145684 1994-01-25 2011-01-25
Canada 2487054 2008-03-18 2023-05-23
Canada 2219475 2002-07-09 2017-12-11
Properties
State solid
Melting point 80.5 oC
Experimental Properties
Property Value Source
water solubility 0.25mg/ml at 25 oC PhysProp
logP 5.3 PhysProp
Predicted Properties
Property Value Source
water solubility 7.07e-04 g/l ALOGPS
logP 4.86 ALOGPS
logP 5.28 ChemAxon Molconvert
logS -5.71 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 52.60 ChemAxon Molconvert
rotatable bond count 7 ChemAxon Molconvert
refractivity 97.13 ChemAxon Molconvert
polarizability 38.15 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Wysocki J, Belowski D, Kalina M, Kochanski L, Okopien B, Kalina Z: Effects of micronized fenofibrate on insulin resistance in patients with metabolic syndrome. Int J Clin Pharmacol Ther. 2004 Apr;42(4):212-7. Pubmed
  2. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesaniemi YA, Sullivan D, Hunt D, Colman P, d’Emden M, Whiting M, Ehnholm C, Laakso M: Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005 Nov 26;366(9500):1849-61. Pubmed
External Links
Resource Link
KEGG Drug D00565 Link_out
KEGG Compound C07586 Link_out
PubChem Compound 3339 Link_out
PubChem Substance 46507371 Link_out
ChemSpider 3222 Link_out
ChEBI 5001 Link_out
ChEMBL 5001 Link_out
Therapeutic Targets Database DAP000270 Link_out
PharmGKB PA449594 Link_out
Drug Product Database 2250039 Link_out
RxList http://www.rxlist.com/cgi/generic3/fenofibrate.htm Link_out
Drugs.com http://www.drugs.com/fenofibrate.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cx1550.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Fenofibrate Link_out
ATC Codes
  • C10AB05
AHFS Codes
  • 24:06.06
PDB Entries Not Available
FDA label show (283 KB)
MSDS show (19.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Increased absorption- take with meals.
Targets

1. Peroxisome proliferator-activated receptor alpha

Pharmacological action: yes
Actions: agonist

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids

Organism class: human
UniProt ID: Q07869 Link_out
Gene: PPARA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Clavey V, Copin C, Mariotte MC, Bauge E, Chinetti G, Fruchart J, Fruchart JC, Dallongeville J, Staels B: Cell culture conditions determine apolipoprotein CIII secretion and regulation by fibrates in human hepatoma HepG2 cells. Cell Physiol Biochem. 1999;9(3):139-49. Pubmed
  2. Chaput E, Saladin R, Silvestre M, Edgar AD: Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. Biochem Biophys Res Commun. 2000 May 10;271(2):445-50. Pubmed
  3. Casas F, Pineau T, Rochard P, Rodier A, Daury L, Dauca M, Cabello G, Wrutniak-Cabello C: New molecular aspects of regulation of mitochondrial activity by fenofibrate and fasting. FEBS Lett. 2000 Sep 29;482(1-2):71-4. Pubmed
  4. Bouly M, Masson D, Gross B, Jiang XC, Fievet C, Castro G, Tall AR, Fruchart JC, Staels B, Lagrost L, Luc G: Induction of the phospholipid transfer protein gene accounts for the high density lipoprotein enlargement in mice treated with fenofibrate. J Biol Chem. 2001 Jul 13;276(28):25841-7. Epub 2001 May 7. Pubmed
  5. Dana SL, Hoener PA, Bilakovics JM, Crombie DL, Ogilvie KM, Kauffman RF, Mukherjee R, Paterniti JR Jr: Peroxisome proliferator-activated receptor subtype-specific regulation of hepatic and peripheral gene expression in the Zucker diabetic fatty rat. Metabolism. 2001 Aug;50(8):963-71. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Guerre-Millo M, Gervois P, Raspe E, Madsen L, Poulain P, Derudas B, Herbert JM, Winegar DA, Willson TM, Fruchart JC, Berge RK, Staels B: Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42. Pubmed

2. Metalloproteinase

Pharmacological action: unknown
Actions: inhibitor
Organism class: human
UniProt ID: O43923 Link_out
Gene: mmp20 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Duhaney TA, Cui L, Rude MK, Lebrasseur NK, Ngoy S, De Silva DS, Siwik DA, Liao R, Sam F: Peroxisome proliferator-activated receptor alpha-independent actions of fenofibrate exacerbates left ventricular dilation and fibrosis in chronic pressure overload. Hypertension. 2007 May;49(5):1084-94. Epub 2007 Mar 12. Pubmed
  2. Lebrasseur NK, Duhaney TA, De Silva DS, Cui L, Ip PC, Joseph L, Sam F: Effects of fenofibrate on cardiac remodeling in aldosterone-induced hypertension. Hypertension. 2007 Sep;50(3):489-96. Epub 2007 Jul 2. Pubmed
Enzymes

1. Cytochrome P450 2C8

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:45

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.