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Identification
NameBezafibrate
Accession NumberDB01393  (DB08380)
TypeSmall Molecule
GroupsApproved
Description

Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [PubChem]

Structure
Thumb
Synonyms
2-(P-(2-(P-Chlorobenzamido)ethyl)phenoxy)-2-methylpropionic acid
Befizal
Bezafibrat
Bezafibrato
Bezafibratum
Bezalip
Bezatol sr (tn)
Cedur
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act-bezafibrate SRtablet (extended-release)400 mgoralActavis Group Ptc EhfNot applicableNot applicableCanada
Bezalip SRtablet (extended-release)400 mgoralActavis Specialty Pharmaceuticals Co1994-12-21Not applicableCanada
Bezalip Tab 200mgtablet200 mgoralHoffmann La Roche Limited1994-12-312001-07-19Canada
Jamp-bezafibrate SRtablet (extended-release)400 mgoralJamp Pharma Corporation2016-04-06Not applicableCanada
PMS-bezafibratetablet200 mgoralPharmascience Inc1999-09-01Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BefizalNot Available
BezalipNot Available
Bezalip retardNot Available
BezatolNot Available
Bezatol SRNot Available
CedurNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIY9449Q51XH
CAS number41859-67-0
WeightAverage: 361.819
Monoisotopic: 361.10808584
Chemical FormulaC19H20ClNO4
InChI KeyInChIKey=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)
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenoxyacetic acid derivatives. These are compounds containing an anisole where the methane group is linked to an acetic acid or a derivative.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenoxyacetic acid derivatives
Direct ParentPhenoxyacetic acid derivatives
Alternative Parents
Substituents
  • Phenoxyacetate
  • 4-halobenzoic acid or derivatives
  • Phenethylamine
  • Benzoic acid or derivatives
  • Benzamide
  • Phenol ether
  • Benzoyl
  • Halobenzene
  • Chlorobenzene
  • Alkyl aryl ether
  • Aryl halide
  • Aryl chloride
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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).
PharmacodynamicsBezafibrate 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 actionLike the other fibrates, bezafibrate is an agonist of PPARα; some studies suggest it may have some activity on PPARγ and PPARδ as well.
Related Articles
AbsorptionBezafibrate is almost completely absorbed after oral administration. The relative bioavailability of bezafibrate retard compared to the standard form is about 70%.
Volume of distributionNot Available
Protein binding94-96% of bezafibrate is bound to protein in human serum.
Metabolism

Hepatic.

Route of eliminationNot Available
Half life1-2 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9246
Blood Brain Barrier+0.8773
Caco-2 permeable-0.5564
P-glycoprotein substrateSubstrate0.6325
P-glycoprotein inhibitor INon-inhibitor0.8387
P-glycoprotein inhibitor IINon-inhibitor0.7329
Renal organic cation transporterNon-inhibitor0.8161
CYP450 2C9 substrateNon-substrate0.7725
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7261
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.883
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5096
Ames testNon AMES toxic0.7749
CarcinogenicityNon-carcinogens0.7815
BiodegradationNot ready biodegradable0.9902
Rat acute toxicity2.4927 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9928
hERG inhibition (predictor II)Non-inhibitor0.6481
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet (extended-release)oral400 mg
Tabletoral200 mg
Prices
Unit descriptionCostUnit
Bezalip 400 mg Sustained-Release Tablet1.96USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point186 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.00155 mg/mLALOGPS
logP3.97ALOGPS
logP3.99ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)3.83ChemAxon
pKa (Strongest Basic)-0.84ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area75.63 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity95.96 m3·mol-1ChemAxon
Polarizability37.53 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Authors unspecified: Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Circulation. 2000 Jul 4;102(1):21-7. [PubMed:10880410 ]
  2. 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:15911729 ]
  3. 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:15123532 ]
  4. 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:16606809 ]
External Links
ATC CodesC10AB02
AHFS Codes
  • 24:06.06
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcipimoxAcipimox may increase the myopathic rhabdomyolysis activities of Bezafibrate.
AtorvastatinBezafibrate may increase the myopathic rhabdomyolysis activities of Atorvastatin.
Chenodeoxycholic acidThe therapeutic efficacy of Chenodeoxycholic acid can be decreased when used in combination with Bezafibrate.
ChlorpropamideBezafibrate may increase the hypoglycemic activities of Chlorpropamide.
CiprofibrateThe risk or severity of adverse effects can be increased when Ciprofibrate is combined with Bezafibrate.
ColchicineBezafibrate may increase the myopathic rhabdomyolysis activities of Colchicine.
ColesevelamColesevelam can cause a decrease in the absorption of Bezafibrate resulting in a reduced serum concentration and potentially a decrease in efficacy.
CyclosporineCyclosporine may increase the nephrotoxic activities of Bezafibrate.
DicoumarolBezafibrate may increase the anticoagulant activities of Dicoumarol.
EzetimibeThe risk or severity of adverse effects can be increased when Bezafibrate is combined with Ezetimibe.
FluvastatinBezafibrate may increase the myopathic rhabdomyolysis activities of Fluvastatin.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Bezafibrate.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Bezafibrate.
LovastatinBezafibrate may increase the myopathic rhabdomyolysis activities of Lovastatin.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Bezafibrate.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Bezafibrate.
PitavastatinBezafibrate may increase the myopathic rhabdomyolysis activities of Pitavastatin.
PravastatinBezafibrate may increase the myopathic rhabdomyolysis activities of Pravastatin.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Bezafibrate.
RaltegravirRaltegravir may increase the myopathic rhabdomyolysis activities of Bezafibrate.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Bezafibrate.
RosuvastatinBezafibrate may increase the myopathic rhabdomyolysis activities of Rosuvastatin.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Bezafibrate.
SimvastatinBezafibrate may increase the myopathic rhabdomyolysis activities of Simvastatin.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Bezafibrate.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Bezafibrate.
Ursodeoxycholic acidThe therapeutic efficacy of Ursodeoxycholic acid can be decreased when used in combination with Bezafibrate.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fa...
Gene Name:
PPARA
Uniprot ID:
Q07869
Molecular Weight:
52224.595 Da
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:10909982 ]
  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:10933891 ]
  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:11172467 ]
  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:11422732 ]
  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:11519881 ]
  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:18629356 ]
  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:16511610 ]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as ...
Gene Name:
PPARD
Uniprot ID:
Q03181
Molecular Weight:
49902.99 Da
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:16168052 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation...
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
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:16168052 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
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.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
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...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates the Na(+)-independent uptake 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. Involved in the clearance of bile acids and organic anions from the liver.
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular Weight:
76447.99 Da
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. doi: 10.3109/00498250903351013. [PubMed:19919292 ]
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Drug created on July 08, 2007 11:01 / Updated on September 16, 2013 17:14