Bezafibrate Explained

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.

It was patented in 1971 and approved for medical use in 1978.[1]

Medical uses

Bezafibrate improves markers of combined hyperlipidemia, effectively reducing LDL and triglycerides and improving HDL levels.[2] The main effect on cardiovascular morbidity is in patients with the metabolic syndrome, the features of which are attenuated by bezafibrate.[3] Studies show that in patients with impaired glucose tolerance, bezafibrate may delay progress to diabetes,[4] and in those with insulin resistance it slowed progress in the HOMA severity marker.[5] 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.[6]

Side-effects

The main toxicity is hepatic (abnormal liver enzymes); myopathy and on rare occasions 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.[7]

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.[8]

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.

Synthesis

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

History

Bezafibrate was first introduced by Boehringer Mannheim in 1977.

Notes and References

  1. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 9783527607495 . 474 . en.
  2. Behar S . Bezafibrate Infarction Prevention (BIP) study . Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease . Circulation . 102 . 1 . 21–27 . July 2000 . 10880410 . 10.1161/01.cir.102.1.21 . free .
  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 . Archives of Internal Medicine . 165 . 10 . 1154–1160 . May 2005 . 15911729 . 10.1001/archinte.165.10.1154 . free .
  4. Tenenbaum A, Motro M, Fisman EZ, Schwammenthal E, Adler Y, Goldenberg I, Leor J, Boyko V, Mandelzweig L, Behar S . 6 . Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease . Circulation . 109 . 18 . 2197–2202 . May 2004 . 15123532 . 10.1161/01.CIR.0000126824.12785.B6 . free .
  5. Tenenbaum A, Fisman EZ, Boyko V, Benderly M, Tanne D, Haim M, Matas Z, Motro M, Behar S . 6 . Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate . Archives of Internal Medicine . 166 . 7 . 737–741 . April 2006 . 16606809 . 10.1001/archinte.166.7.737 . free .
  6. 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 . 11 . 1 . 29 . March 2012 . 22439599 . 3342914 . 10.1186/1475-2840-11-29 . free .
  7. 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 . 6 . Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice . Human Molecular Genetics . 21 . 23 . 5091–5105 . December 2012 . 22922230 . 3490516 . 10.1093/hmg/dds355 .
  8. Web site: Contraceptive, Cholesterol - lowering drugs used to treat cancer. . 14 May 2015 . Science daily.