Bezafibrate: Difference between revisions

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==Uses==
==Uses==
Bezafibrate improves markers of [[combined hyperlipidemia]], effectively reducing LDL and triglycerides and improving HDL levels.<ref>{{cite journal | title = Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study | journal = Circulation | volume = 102 | issue = 1 | pages = 21–7 | year = 2000 | pmid = 10880410 | doi=10.1161/01.cir.102.1.21}}</ref> The main effect on cardiovascular morbidity is in patients with the [[metabolic syndrome]], the features of which are attenuated by bezafibrate.<ref>{{cite journal | last1 = Tenenbaum | first1 = A | last2 = Motro | first2 = M | last3 = Fisman | first3 = EZ | last4 = Tanne | first4 = D | last5 = Boyko | first5 = V | last6 = Behar | first6 = S | title = Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome | journal = Archives of Internal Medicine | volume = 165 | issue = 10 | pages = 1154–60 | year = 2005 | pmid = 15911729 | doi = 10.1001/archinte.165.10.1154 }}</ref> Studies show that in patients with impaired glucose tolerance, bezafibrate may delay progress to diabetes,<ref>{{cite journal | last1 = Tenenbaum | first1 = A | last2 = Motro | first2 = M | last3 = Fisman | first3 = EZ | last4 = Schwammenthal | first4 = E | last5 = Adler | first5 = Y | last6 = Goldenberg | first6 = I | last7 = Leor | first7 = J | last8 = Boyko | first8 = V | last9 = Mandelzweig | first9 = L | last10 = Behar | first10 = S | title = Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease | journal = Circulation | volume = 109 | issue = 18 | pages = 2197–202 | year = 2004 | pmid = 15123532 | doi = 10.1161/01.CIR.0000126824.12785.B6 | display-authors = 8 }}</ref> and in those with [[insulin resistance]] it slowed progress in the [[homeostatic model assessment|HOMA]] severity marker.<ref>{{cite journal | last1 = Tenenbaum | first1 = A | last2 = Fisman | first2 = EZ | last3 = Boyko | first3 = V | last4 = Benderly | first4 = M | last5 = Tanne | first5 = D | last6 = Haim | first6 = M | last7 = Matas | first7 = Z | last8 = Motro | first8 = M | last9 = Behar | first9 = S | title = Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate | journal = Archives of Internal Medicine | volume = 166 | issue = 7 | pages = 737–41 | year = 2006 | pmid = 16606809 | doi = 10.1001/archinte.166.7.737 }}</ref> In addition, a prospective observational study of dyslipidemic patients with diabetes or hyperglycemia showed that bezafibrate significantly reduces haemoglobin A1c (HbA1c) concentration as a function of baseline HbA1c levels, regardless of concurrent use of antidiabetic drugs.<ref>Teramoto T, Shirai K, Daida H, Yamada N. Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study. [[Cardiovascular Diabetology]] 2012, 11:29. http://www.cardiab.com/content/11/1/29, PMID 22439599</ref>
Bezafibrate improves markers of [[combined hyperlipidemia]], effectively reducing LDL and triglycerides and improving HDL levels.<ref>{{cite journal | title = Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study | journal = Circulation | volume = 102 | issue = 1 | pages = 21–7 | year = 2000 | pmid = 10880410 | doi=10.1161/01.cir.102.1.21}}</ref> The main effect on cardiovascular morbidity is in patients with the [[metabolic syndrome]], the features of which are attenuated by bezafibrate.<ref>{{cite journal | last1 = Tenenbaum | first1 = A | last2 = Motro | first2 = M | last3 = Fisman | first3 = EZ | last4 = Tanne | first4 = D | last5 = Boyko | first5 = V | last6 = Behar | first6 = S | title = Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome | journal = Archives of Internal Medicine | volume = 165 | issue = 10 | pages = 1154–60 | year = 2005 | pmid = 15911729 | doi = 10.1001/archinte.165.10.1154 }}</ref> Studies show that in patients with impaired glucose tolerance, bezafibrate may delay progress to diabetes,<ref>{{cite journal | last1 = Tenenbaum | first1 = A | last2 = Motro | first2 = M | last3 = Fisman | first3 = EZ | last4 = Schwammenthal | first4 = E | last5 = Adler | first5 = Y | last6 = Goldenberg | first6 = I | last7 = Leor | first7 = J | last8 = Boyko | first8 = V | last9 = Mandelzweig | first9 = L | last10 = Behar | first10 = S | title = Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease | journal = Circulation | volume = 109 | issue = 18 | pages = 2197–202 | year = 2004 | pmid = 15123532 | doi = 10.1161/01.CIR.0000126824.12785.B6 | display-authors = 8 }}</ref> and in those with [[insulin resistance]] it slowed progress in the [[homeostatic model assessment|HOMA]] severity marker.<ref>{{cite journal | last1 = Tenenbaum | first1 = A | last2 = Fisman | first2 = EZ | last3 = Boyko | first3 = V | last4 = Benderly | first4 = M | last5 = Tanne | first5 = D | last6 = Haim | first6 = M | last7 = Matas | first7 = Z | last8 = Motro | first8 = M | last9 = Behar | first9 = S | title = Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate | journal = Archives of Internal Medicine | volume = 166 | issue = 7 | pages = 737–41 | year = 2006 | pmid = 16606809 | doi = 10.1001/archinte.166.7.737 }}</ref> In addition, a prospective observational study of dyslipidemic patients with diabetes or hyperglycemia showed that bezafibrate significantly reduces haemoglobin A1c (HbA1c) concentration as a function of baseline HbA1c levels, regardless of concurrent use of antidiabetic drugs.<ref>{{cite journal | url = http://www.cardiab.com/content/11/1/29, | pmid = 22439599 | doi=10.1186/1475-2840-11-29 | volume=11 | title=Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study | pmc=3342914 | issue=1 | year=2012 | journal=Cardiovasc Diabetol | page=29 | last1 = Teramoto | first1 = T | last2 = Shirai | first2 = K | last3 = Daida | first3 = H | last4 = Yamada | first4 = N}}</ref>


==Side-effects==
==Side-effects==
Line 66: Line 66:
The Australian biotech company [[Giaconda (pharmaceutical company)|Giaconda]] combines bezafibrate with [[chenodeoxycholic acid]] in an anti-[[hepatitis C]] drug combination called Hepaconda.
The Australian biotech company [[Giaconda (pharmaceutical company)|Giaconda]] combines bezafibrate with [[chenodeoxycholic acid]] in an anti-[[hepatitis C]] drug combination called Hepaconda.


Bezafibrate has been shown to reduce [[tau protein]] [[Phosphorylation|hyperphosphorylation]] and other signs of [[tauopathy]] in [[Genetically modified mouse|transgenic mice]] having human tau [[mutation]].<ref>{{cite journal |vauthors=Dumont M, Stack C, Elipenahli C, Jainuddin S, Gerges M, Starkova N, Calingasan NY, Yang L, Tampellini D, Starkov AA, Chan RB, Di Paolo G, Pujol A, Beal MF | title=Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice | journal=[[Human Molecular Genetics]] | volume=21 | issue=23 | year=2012 | pages=5091–5105 | doi = 10.1093/hmg/dds355 | id= | pmid=22922230}}</ref>
Bezafibrate has been shown to reduce [[tau protein]] [[Phosphorylation|hyperphosphorylation]] and other signs of [[tauopathy]] in [[Genetically modified mouse|transgenic mice]] having human tau [[mutation]].<ref>{{cite journal |vauthors=Dumont M, Stack C, Elipenahli C, Jainuddin S, Gerges M, Starkova N, Calingasan NY, Yang L, Tampellini D, Starkov AA, Chan RB, Di Paolo G, Pujol A, Beal MF | title=Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice | journal=[[Human Molecular Genetics]] | volume=21 | issue=23 | year=2012 | pages=5091–5105 | doi = 10.1093/hmg/dds355 | id= | pmid=22922230 | pmc=3490516}}</ref>


The combination of a cholesterol-lowering drug, bezafibrate, and a contraceptive steroid, medroxyprogesterone acetate, could be an effective, non-toxic treatment for a range of cancers, researchers at the University of Birmingham have found.<ref>{{Cite web|url = http://www.sciencedaily.com/releases/2015/05/150514102813.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily%2Fmost_popular+%28Most+Popular+News+--+ScienceDaily%29|title = Contraceptive,Cholestrol - lowering drugs used to treat cancer. - Science daily|date = |accessdate = |website = |publisher = }}</ref>
The combination of a cholesterol-lowering drug, bezafibrate, and a contraceptive steroid, medroxyprogesterone acetate, could be an effective, non-toxic treatment for a range of cancers, researchers at the University of Birmingham have found.<ref>{{Cite web|url = http://www.sciencedaily.com/releases/2015/05/150514102813.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily%2Fmost_popular+%28Most+Popular+News+--+ScienceDaily%29|title = Contraceptive,Cholestrol - lowering drugs used to treat cancer. - Science daily|date = |accessdate = |website = |publisher = }}</ref>

Revision as of 05:47, 4 May 2017

Bezafibrate
Clinical data
AHFS/Drugs.comInternational Drug Names
MedlinePlusa682711
Routes of
administration		Oral
ATC code
Legal status
Legal status
Identifiers
  • 2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.050.498 Edit this at Wikidata
Chemical and physical data
FormulaC19H20ClNO4
Molar mass361.819 g/mol g·mol−1
3D model (JSmol)
  • O=C(c1ccc(Cl)cc1)NCCc2ccc(OC(C(=O)O)(C)C)cc2
  • 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) checkY
  • Key:IIBYAHWJQTYFKB-UHFFFAOYSA-N checkY
  (verify)

Bezafibrate (marketed as Bezalip and various other brand names) is a fibrate drug used as a lipid-lowering agent to treat hyperlipidaemia. It helps to lower LDL cholesterol and triglyceride in the blood, and increase HDL.

History

Bezafibrate was first introduced by Boehringer Mannheim in 1977.

Mode 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.

Uses

Bezafibrate improves markers of combined hyperlipidemia, effectively reducing LDL and triglycerides and improving HDL levels.[1] The main effect on cardiovascular morbidity is in patients with the metabolic syndrome, the features of which are attenuated by bezafibrate.[2] Studies show that in patients with impaired glucose tolerance, bezafibrate may delay progress to diabetes,[3] and in those with insulin resistance it slowed progress in the HOMA severity marker.[4] In addition, a prospective observational study of dyslipidemic patients with diabetes or hyperglycemia showed that bezafibrate significantly reduces haemoglobin A1c (HbA1c) concentration as a function of baseline HbA1c levels, regardless of concurrent use of antidiabetic drugs.[5]

Side-effects

The main toxicity is hepatic (abnormal liver enzymes), and myopathy and rarely rhabdomyolysis have been reported.

Other uses

The Australian biotech company Giaconda combines bezafibrate with chenodeoxycholic acid in an anti-hepatitis C drug combination called Hepaconda.

Bezafibrate has been shown to reduce tau protein hyperphosphorylation and other signs of tauopathy in transgenic mice having human tau mutation.[6]

The combination of a cholesterol-lowering drug, bezafibrate, and a contraceptive steroid, medroxyprogesterone acetate, could be an effective, non-toxic treatment for a range of cancers, researchers at the University of Birmingham have found.[7]

Synthesis

Further evidence that substantial bulk tolerance is available in the para position is given by the lipid lowering agent bezafibrate.

Bezafibrate synthesis: E. Witte et al., DE 2149070 ; eidem, U.S. patent 3,781,328 (both 1973 to Boehringer, Mann.).

The p-chlorobenzamide of tyramine undergoes a Williamson ether synthesis with ethyl 2-bromo-2-methylpropionate to complete the synthesis. The ester group is hydrolyzed in the alkaline reaction medium.

References

  1. ^ "Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study". Circulation. 102 (1): 21–7. 2000. doi:10.1161/01.cir.102.1.21. PMID 10880410.
  2. ^ Tenenbaum, A; Motro, M; Fisman, EZ; Tanne, D; Boyko, V; Behar, S (2005). "Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome". Archives of Internal Medicine. 165 (10): 1154–60. doi:10.1001/archinte.165.10.1154. PMID 15911729.
  3. ^ Tenenbaum, A; Motro, M; Fisman, EZ; Schwammenthal, E; Adler, Y; Goldenberg, I; Leor, J; Boyko, V; et al. (2004). "Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease". Circulation. 109 (18): 2197–202. doi:10.1161/01.CIR.0000126824.12785.B6. PMID 15123532.
  4. ^ Tenenbaum, A; Fisman, EZ; Boyko, V; Benderly, M; Tanne, D; Haim, M; Matas, Z; Motro, M; Behar, S (2006). "Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate". Archives of Internal Medicine. 166 (7): 737–41. doi:10.1001/archinte.166.7.737. PMID 16606809.
  5. ^ Teramoto, T; Shirai, K; Daida, H; Yamada, N (2012). "Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study". Cardiovasc Diabetol. 11 (1): 29. doi:10.1186/1475-2840-11-29. PMC 3342914. PMID 22439599.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Dumont M, Stack C, Elipenahli C, Jainuddin S, Gerges M, Starkova N, Calingasan NY, Yang L, Tampellini D, Starkov AA, Chan RB, Di Paolo G, Pujol A, Beal MF (2012). "Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice". Human Molecular Genetics. 21 (23): 5091–5105. doi:10.1093/hmg/dds355. PMC 3490516. PMID 22922230.
  7. ^ "Contraceptive,Cholestrol - lowering drugs used to treat cancer. - Science daily".
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