Clofibrate

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Clofibrate
Clofibrate.svg
Clinical data
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Pregnancy
category
  • AU:B1
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • US:Discontinued
Pharmacokinetic data
Protein binding Variable, 92–97% at therapeutic concentrations
Metabolism Hydrolyzed to clofibric acid; hepatic glucuronidation
Elimination half-life Highly variable; average 18–22 hours. Prolonged in renal failure
Excretion Renal, 95 to 99%
Identifiers
  • ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.010.253 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H15ClO3
Molar mass 242.70 g·mol−1
3D model (JSmol)
Boiling point 148 °C (298 °F)
  • Clc1ccc(OC(C(=O)OCC)(C)C)cc1
  • InChI=1S/C12H15ClO3/c1-4-15-11(14)12(2,3)16-10-7-5-9(13)6-8-10/h5-8H,4H2,1-3H3 Yes check.svgY
  • Key:KNHUKKLJHYUCFP-UHFFFAOYSA-N Yes check.svgY
   (verify)

Clofibrate (trade name Atromid-S) is a lipid-lowering agent used for controlling the high cholesterol and triacylglyceride level in the blood. It belongs to the class of fibrates. It increases lipoprotein lipase activity to promote the conversion of VLDL to LDL, and hence reduce the level of VLDL. It can increase the level of HDL as well.

It was patented in 1958 by Imperial Chemical Industries and approved for medical use in 1963. [1] Clofibrate was discontinued in 2002 due to adverse effects.

Complications and controversies

It can induce SIADH, syndrome of inappropriate secretion of antidiuretic hormone ADH (vasopressin). Clofibrate can also result in formation of cholesterol stones in the gallbladder.

The World Health Organization Cooperative Trial on Primary Prevention of Ischaemic Heart Disease using clofibrate to lower serum cholesterol observed excess mortality in the clofibrate-treated group despite successful cholesterol lowering (47% more deaths during treatment with clofibrate and 5% after treatment with clofibrate) than the non-treated high cholesterol group. These deaths were due to a wide variety of causes other than heart disease, and remain "unexplained". [2]

Related Research Articles

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Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the cardiac muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, and myocardial infarction.

<span class="mw-page-title-main">Cholesterol</span> Sterol biosynthesized by all animal cells

Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.

High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.

<span class="mw-page-title-main">Low-density lipoprotein</span> One of the five major groups of lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL has been associated with the progression of atherosclerosis.

<span class="mw-page-title-main">Statin</span> Class of drugs to lower cholesterol

Statins are a class of medications that reduce illness and mortality in people who are at high risk of cardiovascular disease.

<span class="mw-page-title-main">Fibrate</span> Class of chemical compounds

In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid. They are used for a range of metabolic disorders, mainly hypercholesterolemia, and are therefore hypolipidemic agents.

<span class="mw-page-title-main">Cardiovascular disease</span> Class of diseases that involve the heart or blood vessels

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<span class="mw-page-title-main">Hypercholesterolemia</span> High levels of cholesterol in the blood

Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.

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Atorvastatin is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.

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<span class="mw-page-title-main">Torcetrapib</span> Chemical compound

Torcetrapib was a drug being developed to treat hypercholesterolemia and prevent cardiovascular disease. Its development was halted in 2006 when phase III studies showed excessive all-cause mortality in the treatment group receiving a combination of atorvastatin (Lipitor) and torcetrapib.

<span class="mw-page-title-main">Fenofibrate</span> Drug of the fibrate class, mainly used to reduce cholesterol levels

Fenofibrate, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared than statins because it treats a different type of cholesterol abnormality to statins. While statins have strong evidence for reducing heart disease and death, there is evidence to suggest that fenofibrate also reduces the risk of heart disease and death. However, this seems only to apply to specific populations of people with elevated triglyceride levels and reduced high-density lipoprotein (HDL) cholesterol. Its use is recommended together with dietary changes.

<span class="mw-page-title-main">Hypocholesterolemia</span> Medical condition

Hypocholesterolemia is the presence of abnormally low (hypo-) levels of cholesterol in the blood (-emia). A defect in the body's production of cholesterol can lead to adverse consequences as well. Cholesterol is an essential component of mammalian cell membranes and is required to establish proper membrane permeability and fluidity. It is not clear if a lower than average cholesterol level is directly harmful; however, it is often encountered in particular illnesses.

<span class="mw-page-title-main">Familial hypercholesterolemia</span> Genetic disorder characterized by high cholesterol levels

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.

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A lipid profile or lipid panel is a panel of blood tests used to find abnormalities in blood lipid concentrations. The results of this test can identify certain genetic diseases and can determine approximate risks for cardiovascular disease, certain forms of pancreatitis, and other diseases.

The vertical auto profile (VAP) test is a cholesterol, lipid and lipoprotein test.

The West of Scotland Coronary Prevention Study was a landmark randomized controlled trial, published in 1995, that investigated the effects of pravastatin, a cholesterol-lowering drug, on primary prevention of coronary heart disease (CHD) in men with hypercholesterolemia. Conducted in the early 1990s, this study provided critical evidence on the benefits of statins in reducing cardiovascular events in individuals without a history of CHD. It concluded that statin treatment reduced CHD events by 31% after nearly five years of treatment.

References

  1. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 474. ISBN   9783527607495.
  2. "WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Report of the Committee of Principal Investigators". Lancet. 2 (8403): 600–4. September 1984. doi:10.1016/s0140-6736(84)90595-6. PMID   6147641. S2CID   2473318.