Gemfibrozil, sold under the brand name Lopid among others, is a medication used to treat
abnormal blood lipid levels.
[ It is generally less preferred than statins.][ Use is recommended together with dietary changes and exercise.][ It is unclear if it changes the risk of ]heart disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
.[ It is taken by mouth.][
Common side effects include headache, dizziness, feeling tired, and intestinal upset.][ Serious side effects may include ]angioedema
Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which ...
, gallstones
A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of mi ...
, liver problems
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the s ...
, and muscle breakdown.[ Use in ]pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
and breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
is of unclear safety.fibrates
In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid (phenoxyisobutyric acid). They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), ...
group of medications and works by decreasing the breakdown of lipids in fat cells
Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...
.generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
.
Medical uses
*Hyperlipidemia
Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbre ...
(Type III)
*Hypertriglyceridemia
Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and h ...
(Type IV): Gemfibrozil, though not as effective as niacin
Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...
(nicotinic acid
Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...
, a form of Vitamin B3
Vitamin B3, colloquially referred to as niacin, is a vitamin family that includes three forms or vitamers: niacin (nicotinic acid), nicotinamide (niacinamide), and nicotinamide riboside. All three forms of vitamin B3 are converted within the bo ...
), is better tolerated.
*Reduce triglyceride
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride'').
Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...
levels
*Reduce very low density lipoprotein
Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lipo ...
(VLDL) levels
*Modest reduction of low density 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 (aka ULDL by the overall density ...
(LDL) levels
*Moderate increase in high density lipoprotein
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 ty ...
(HDL) levels
Side effects
*GI distress
*Musculoskeletal pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
*Increased incidence of gallstone
A gallstone is a calculus (medicine), stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to ...
*Hypokalemia
Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
(low blood potassium)
*Increased risk of cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
Contraindications
*Gemfibrozil should not be given to these patients:
**Hepatic dysfunction
*Gemfibrozil should be used with caution in these higher risk categories:
**Biliary tract disease
**Renal dysfunction
**Pregnant women
**Obese patients
Drug interactions
*Anticoagulants: Gemfibrozil potentiates the action of warfarin
Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...
and indanedione anticoagulants.
*Statin drugs: Concomitant administration of fibrates (including gemfibrozil) with statin drugs increases the risk of muscle cramping, myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
, and rhabdomyolysis
Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of th ...
.
*Gemfibrozil inhibits the activation of the liver's Cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
system and CYP2C8, reducing hepatic
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...
metabolism of many drugs, and prolonging their half lives and duration of action.
** Drugs metabolized by the Cytochrome P450 system include:
*** Many antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
s
*** Many antipsychotic
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
s
*** Many antiepileptic
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s
*** Theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
and other methylxanthine drugs
*** Several anesthetic agents
*** Oral contraceptive pill Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control.
Female
Two types of female oral contraceptive pill, taken once per day, are widely available:
* The combin ...
s
*** Statin
Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs.
Low- ...
s
*** Warfarin
Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...
*** Selexipag
Mechanism of actions
The exact mechanism of action of gemfibrozil is unknown; however, several theories exist regarding the very low density lipoprotein (VLDL) effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels and increase HDL-cholesterol; the mechanism behind HDL elevation is currently unknown.
Gemfibrozil increases the activity of extrahepatic lipoprotein lipase
Lipoprotein lipase (LPL) (EC 3.1.1.34, systematic name triacylglycerol acylhydrolase (lipoprotein-dependent)) is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water-soluble ...
(LL), thereby increasing lipoprotein triglyceride lipolysis. It does so by activating peroxisome proliferator-activated receptor alpha
Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the ''PPARA'' gene ...
(PPARα) 'transcription factor ligand', a receptor that is involved in metabolism of carbohydrates and fats, as well as adipose tissue differentiation. This increase in the synthesis of lipoprotein lipase thereby increases the clearance of triglycerides. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Gemfibrozil also inhibits the synthesis and increases the clearance of apolipoprotein B
Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene.
Function
Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, Lp(a), IDL, and LDL particles (LDL—commonly known as "bad cholesterol" when in refer ...
, a carrier molecule for VLDL.
History
Gemfibrozil was selected from a series of related compounds synthesized in the laboratories of the American company Parke-Davis
Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although Parke, Davis & Co. is no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history. In 1970 ...
in the late 1970s. It came from research for compounds that lower plasma lipid levels in humans and in animals.
Environmental data
Gemfibrozil has been detected in biosolids
Biosolids are solid organic matter recovered from a sewage treatment process and used as fertilizer. In the past, it was common for farmers to use animal manure to improve their soil fertility. In the 1920s, the farming community began also to use ...
(the solids remaining after sewage treatment
Sewage treatment (or domestic wastewater treatment, municipal wastewater treatment) is a type of wastewater treatment which aims to remove contaminants from sewage to produce an effluent that is suitable for discharge to the surrounding envir ...
) at concentrations up to 2650 ng/g wet weight. This indicates that it survives the wastewater treatment
Wastewater treatment is a process used to remove contaminants from wastewater and convert it into an effluent that can be returned to the water cycle. Once returned to the water cycle, the effluent creates an acceptable impact on the environme ...
process. It is also detected as environmental persistent micropollutant in aquifer
An aquifer is an underground layer of water-bearing, permeable rock, rock fractures, or unconsolidated materials (gravel, sand, or silt). Groundwater from aquifers can be extracted using a water well. Aquifers vary greatly in their characterist ...
s and in groundwater
Groundwater is the water present beneath Earth's surface in rock and soil pore spaces and in the fractures of rock formations. About 30 percent of all readily available freshwater in the world is groundwater. A unit of rock or an unconsolidate ...
s in karst
Karst is a topography formed from the dissolution of soluble rocks such as limestone, dolomite, and gypsum. It is characterized by underground drainage systems with sinkholes and caves. It has also been documented for more weathering-resistant ro ...
ic areas.
References
Further reading
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External links
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Fibrates
Phenol ethers
Carboxylic acids
CYP2C8 inhibitors