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Identification
Name Bezafibrate
Accession Number DB01393 (DB08380)
Type small molecule
Groups approved
Description

Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Bezafibrat
  • Bezafibrato [inn-spanish]
  • Bezafibratum [inn-latin]
Synonyms
Bezafibrat
Bezafibrato [inn-spanish]
Bezafibratum [inn-latin]
Salts Not Available
Brand names
Name Company
Befizal
Bezalip
Bezalip retard
Bezatol
Bezatol SR
Cedur
Brand mixtures
Brand Name Ingredients
Hepaconda bezafibrate + chenodeoxycholic acid
Categories
  • Antilipemic Agents
CAS number 41859-67-0
Weight Average: 361.819
Monoisotopic: 361.10808584
Chemical Formula C19H20ClNO4
InChI Key InChIKey=IIBYAHWJQTYFKB-UHFFFAOYSA-N
InChI
InChI=1S/C19H20ClNO4/c1-19(2,18(23)24)25-16-9-3-13(4-10-16)11-12-21-17(22)14-5-7-15(20)8-6-14/h3-10H,11-12H2,1-2H3,(H,21,22)(H,23,24)
Plain Text
IUPAC Name
2-(4-{2-[(4-chlorophenyl)formamido]ethyl}phenoxy)-2-methylpropanoic acid
SMILES
CC(C)(OC1=CC=C(CCNC(=O)C2=CC=C(Cl)C=C2)C=C1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenoxyacetates
Substructures
  • Hydroxy Compounds
  • Acetates
  • Phenols and Derivatives
  • Amino Ketones
  • Phenoxyacetates
  • Short-chain Hydroxy Acids
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Phenethylamines
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Phenyl Esters
  • Benzamides
Pharmacology
Indication For the treatment of primary hyperlipidaemia types IIa, IIb, III, IV and V (Fredrickson classification) corresponding to groups I, II and III of the European Atherosclerosis Society guidelines - when diet alone or improvements in lifestyle such as increased exercise or weight reduction do not lead to an adequate response. Also for the treatment of secondary hyperlipidaemias, e.g. severe hypertriglyceridemias, when sufficient improvement does not occur after correction of the underlying disorder (e.g. diabetes mellitus).
Pharmacodynamics Bezafibrate is an antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. Bezafibrate lowers elevated blood lipids (triglycerides and cholesterol). Elevated VLDL and LDL are reduced by treatment with bezafibrate, whilst HDL-levels are increased. The activity of triglyceride lipases (lipoprotein lipase and hepatic lipoproteinlipase) involved in the catabolism of triglyceride-rich lipoproteins is increased by bezafibrate. In the course of the intensified degradation of triglyceride-rich lipoproteins (chylomicrons, VLDL) precursors for the formation of HDL are formed which explains an increase in HDL. Furthermore, cholesterol biosynthesis is reduced by bezafibrate, which is accompanied by a stimulation of the LDL-receptor-mediated lipoprotein catabolism. Elevated fibrinogen appears to be an important risk-factor, alongside the lipids, smoking and hypertension, in the development of atheroma. Fibrinogen plays an important role in viscosity, and therefore blood flow, and also appears to play an important role in thrombus development and lysability. Bezafibrate exerts an effect on thrombogenic factors. A significant decrease in elevated plasma fibrinogen levels can be achieved. This may lead, amongst other things, to a reduction in both blood and plasma viscosity. Inhibition of platelet aggregation has also been observed. A reduction in blood glucose concentration due to an increase in glucose tolerance has been reported in diabetic patients. In the same patients, the concentration of fasting and postprandial free fatty acids was reduced by bezafibrate.
Mechanism of action Like the other fibrates, bezafibrate is an agonist of PPARα; some studies suggest it may have some activity on PPARγ and PPARδ as well.
Absorption Bezafibrate is almost completely absorbed after oral administration. The relative bioavailability of bezafibrate retard compared to the standard form is about 70%.
Volume of distribution Not Available
Protein binding 94-96% of bezafibrate is bound to protein in human serum.
Metabolism Hepatic.
Route of elimination Not Available
Half life 1-2 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms
Form Route Strength
Tablet Oral
Tablet Oral 200mg
Tablet, extended release Oral
Tablet, film coated, extended release Oral 400mg
Prices
Unit description Cost Unit
Bezalip 400 mg Sustained-Release Tablet 1.96 USD tablet
Patents Not Available
Properties
State solid
Melting point 186 oC
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 1.55e-03 g/l ALOGPS
logP 3.97 ALOGPS
logP 3.99 ChemAxon Molconvert
logS -5.4 ALOGPS
pKa 14.75 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 75.63 ChemAxon Molconvert
rotatable bond count 7 ChemAxon Molconvert
refractivity 95.96 ChemAxon Molconvert
polarizability 37.53 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Link
  2. : Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000 Jul 4;102(1):21-7. Pubmed
  3. Tenenbaum A, Motro M, Fisman EZ, Tanne D, Boyko V, Behar S: Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med. 2005 May 23;165(10):1154-60. Pubmed
  4. Tenenbaum A, Motro M, Fisman EZ, Schwammenthal E, Adler Y, Goldenberg I, Leor J, Boyko V, Mandelzweig L, Behar S: Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease. Circulation. 2004 May 11;109(18):2197-202. Epub 2004 May 3. Pubmed
  5. Tenenbaum A, Fisman EZ, Boyko V, Benderly M, Tanne D, Haim M, Matas Z, Motro M, Behar S: Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Intern Med. 2006 Apr 10;166(7):737-41. Pubmed
External Links
Resource Link
KEGG Drug D01366 Link_out
PubChem Compound 39042 Link_out
PubChem Substance 46509188 Link_out
ChemSpider 35728 Link_out
BindingDB 28701 Link_out
ChEBI 47612 Link_out
ChEMBL 47612 Link_out
Therapeutic Targets Database DAP001182 Link_out
IUPHAR 2668 Link_out
Guide to Pharmacology 2668 Link_out
HET PEM Link_out
Drug Product Database 2083523 Link_out
Wikipedia http://en.wikipedia.org/wiki/Bezafibrate Link_out
ATC Codes
  • C10AB02
AHFS Codes
  • 24:06.06
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Atorvastatin Increased risk of myopathy/rhabdomyolysis
Cerivastatin Increased risk of myopathy/rhabdomyolysis
Cholestyramine Bile acid sequestrants like cholestyramine may decrease the absorption of fibric acid derivatives like bezafibrate. Therapy modification should be considered. If concomitant therapy is used, separate doses by at least 2 hours to minimize this interaction. Fenofibric acid labeling recommends administration one hour prior to or 4-6 hours after a bile acid sequestrant.
Conivaptan Conivaptan may increase the serum concentration of CYP3A4 substrates like bezafibrates. Consider therapy modification. Conivaptan may increase the serum concentration of CYP3A4 substrates.
Cyclosporine Cyclosporine may enhance the nephrotoxic effect of fibric acid derivatives like bezafibrate. Fibric acid derivatives may decrease the serum concentration of cyclosporine. Extra monitoring of renal function and cyclosporine concentrations will likely be required. Adjustment of cyclosporine dose may be necessary.
Fluvastatin Increased risk of myopathy/rhabdomyolysis
Isocarboxazid MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like isocarboxazid.
Linezolid MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like linezolid.
Lovastatin Increased risk of myopathy/rhabdomyolysis
Moclobemide MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like moclobemide.
Phenelzine MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like phenelzine.
Pravastatin Increased risk of myopathy/rhabdomyolysis
Procarbazine MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like procarbazine.
Rasagiline MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) rasagiline.
Selegiline MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like selegiline.
Tranylcypromine MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like tranylcypromine.
Warfarin Bezafibrate may increase the anticoagulant effect of warfarin. Monitor prothrombin time and therapeutic and adverse effects of warfarin if bezafibrate is initiated, discontinued or dose changed.
Food Interactions Not Available
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. Pedraza N, Solanes G, Carmona MC, Iglesias R, Vinas O, Mampel T, Vazquez M, Giralt M, Villarroya F: Impaired expression of the uncoupling protein-3 gene in skeletal muscle during lactation: fibrates and troglitazone reverse lactation-induced downregulation of the uncoupling protein-3 gene. Diabetes. 2000 Jul;49(7):1224-30. Pubmed
  2. Cabrero A, Alegret M, Sanchez R, Adzet T, Laguna JC, Vazquez M: Peroxisome proliferator-activated receptor alpha (PPARalpha) activators, bezafibrate and Wy-14,643, increase uncoupling protein-3 mRNA levels without modifying the mitochondrial membrane potential in primary culture of rat preadipocytes. Arch Biochem Biophys. 2000 Aug 15;380(2):353-9. Pubmed
  3. Inoue I, Goto S, Matsunaga T, Nakajima T, Awata T, Hokari S, Komoda T, Katayama S: The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+,Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells. Metabolism. 2001 Jan;50(1):3-11. Pubmed
  4. Guan Y, Breyer MD: Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease. Kidney Int. 2001 Jul;60(1):14-30. Pubmed
  5. Bonilla S, Redonnet A, Noel-Suberville C, Groubet R, Pallet V, Higueret P: Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver. J Physiol Biochem. 2001 Mar;57(1):1-8. Pubmed
  6. Goldenberg I, Benderly M, Goldbourt U: Update on the use of fibrates: focus on bezafibrate. Vasc Health Risk Manag. 2008;4(1):131-41. Pubmed
  7. Fruchart JC, Duriez P: Mode of action of fibrates in the regulation of triglyceride and HDL-cholesterol metabolism. Drugs Today (Barc). 2006 Jan;42(1):39-64. Pubmed
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Peroxisome proliferator-activated receptor delta

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. Decreases expression of NPC1L1 once activated by a ligand

Organism class: human
UniProt ID: Q03181 Link_out
Gene: PPARD Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tenenbaum A, Motro M, Fisman EZ: Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc Diabetol. 2005 Sep 16;4:14. Pubmed

3. Peroxisome proliferator-activated receptor gamma

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. Key regulator of adipocyte differentiation and glucose homeostasis

Organism class: human
UniProt ID: P37231 Link_out
Gene: PPARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tenenbaum A, Motro M, Fisman EZ: Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc Diabetol. 2005 Sep 16;4:14. Pubmed
Enzymes

1. Cytochrome P450 1A1

Actions: inducer

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

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
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

2. 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. 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
Transporters

1. Solute carrier organic anion transporter family member 1B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sharma P, Holmes VE, Elsby R, Lambert C, Surry D: Validation of cell-based OATP1B1 assays to assess drug transport and the potential for drug-drug interaction to support regulatory submissions. Xenobiotica. 2010 Jan;40(1):24-37. Pubmed
Comments
Drug created on July 08, 2007 11:01 / Updated on February 14, 2012 11:47