Chemistry:Bezafibrate
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| AHFS/Drugs.com | International Drug Names |
| MedlinePlus | a682711 |
| Routes of administration | Oral |
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| Formula | C19H20ClNO4 |
| Molar mass | 361.82 g·mol−1 |
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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.
References
- ↑ (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 474. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA474.
- ↑ "Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease". Circulation 102 (1): 21–27. July 2000. doi:10.1161/01.cir.102.1.21. PMID 10880410.
- ↑ "Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome". Archives of Internal Medicine 165 (10): 1154–1160. May 2005. doi:10.1001/archinte.165.10.1154. PMID 15911729.
- ↑ "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. doi:10.1161/01.CIR.0000126824.12785.B6. PMID 15123532.
- ↑ "Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate". Archives of Internal Medicine 166 (7): 737–741. April 2006. doi:10.1001/archinte.166.7.737. PMID 16606809.
- ↑ "Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study". Cardiovascular Diabetology 11 (1): 29. March 2012. doi:10.1186/1475-2840-11-29. PMID 22439599.
- ↑ "Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice". Human Molecular Genetics 21 (23): 5091–5105. December 2012. doi:10.1093/hmg/dds355. PMID 22922230.
- ↑ "Contraceptive, Cholesterol - lowering drugs used to treat cancer.". Science daily. 14 May 2015. https://www.sciencedaily.com/releases/2015/05/150514102813.htm.
- ↑ Witte EC, Stach K, Stork H, Thiel M, Schmidt F, "Phenoxyalkylcarbonsäurederivate und Verfahren zur Herstellung derselben [Phenoxyalkylcarboxylic acid derivatives and processes for the production of the same]", DE patent 2149070, published 1973-04-05, issued 23 April 1978, assigned to Boehringer Mannheim GmbH
- ↑ Witte EC, Stach K, Stork H, Thiel M, Schmidt F, "Phenoxy-alkyl-carboxylic acid compounds", US patent 3781328, issued 25 December 1973
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