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
Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease.
Low-density lipoprotein (LDL) carriers of cholesterol play ...
.[ Use is recommended together with dietary changes and exercise.][ It is unclear if it changes the risk of ]heart disease
Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
.[ 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 are ...
, 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 ...
, 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.
Liver diseases
File:Ground gla ...
, and muscle breakdown.[ Use in ]pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
and breastfeeding
Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...
is of unclear safety.fibrates
In pharmacology, the fibrates are a class of Amphiphile, amphipathic carboxylic acids and esters. They are derivatives of fibric acid (phenoxyisobutyric acid). They are used for a range of metabolism, metabolic disorders, mainly hypercholesterole ...
group of medications and works by decreasing the breakdown of lipids in fat cells
Adipocytes, also known as lipocytes and fat cells, are the cell (biology), 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 ...
.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 high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...
(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 ...
(Type IV): Gemfibrozil, though not as effective as niacin (nicotinic acid
Nicotinic acid, or niacin, is an organic compound and a vitamer of vitamin B3, an essential human nutrient. It is produced by plants and animals from the amino acid tryptophan.
Nicotinic acid is also a prescription medication. Amounts f ...
, a form of Vitamin B3
Vitamin B3, colloquially referred to as niacin, is a vitamin family that includes three forms, or vitamers: nicotinic acid (niacin), nicotinamide (niacinamide), and nicotinamide riboside. All three forms of vitamin B3 are converted within th ...
), is better tolerated.
*Reduce triglyceride
A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids.
Triglycerides are the main constituents of body fat in humans and other vertebrates ...
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 li ...
(VLDL) levels
*Modest reduction of low density lipoprotein (LDL) levels
*Moderate increase in high density lipoprotein (HDL) levels
Side effects
*GI distress
*Musculoskeletal pain
Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
*Increased incidence of gallstone
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 ...
*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 a ...
(low blood potassium)
*Increased risk of cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
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. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...
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. ''Myopathy'' means muscle disease ( Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meaning implies that the primary defec ...
, and rhabdomyolysis
Rhabdomyolysis (shortened as 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 o ...
.
*Gemfibrozil inhibits the activation of the liver's Cytochrome P450
Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...
system and CYP2C8, reducing hepatic
The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
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 medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.
Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...
s
*** Many antipsychotic
Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...
s
*** Many antiepileptic
Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatmen ...
s
*** Theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a drug that inhibits phosphodiesterase and blocks adenosine receptors. It is used to treat chronic obstructive pulmonary disease (COPD) and asthma. Its pharmacology is similar to other met ...
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. The introduction of the birth control pill ("the Pill") in 1960 revolutionized the options for contraception, ...
s
*** Statin
Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease.
Low-density lipoprotein (LDL) carriers of cholesterol play ...
s
*** Warfarin
Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...
*** 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-solubl ...
(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'' gen ...
(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. Its measurement is commonly used to detect the risk of Atherosclerosis, atherosclerotic Coronary artery disease, cardiovascular disease.
Isoforms
The protein occur ...
, 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 us ...
(the solids remaining after sewage treatment
Sewage treatment is a type of wastewater treatment which aims to remove contaminants from sewage to produce an effluent that is suitable to discharge to the surrounding environment or an intended reuse application, thereby preventing water p ...
) at concentrations up to 2650 ng/g wet weight. This indicates that it survives the wastewater treatment
Wastewater treatment is a process which removes and eliminates contaminants from wastewater. It thus converts it into an effluent that can be returned to the water cycle. Once back in the water cycle, the effluent creates an acceptable impact on ...
process. It is also detected as environmental persistent micropollutant in aquifer
An aquifer is an underground layer of water-bearing material, consisting of permeability (Earth sciences), permeable or fractured rock, or of unconsolidated materials (gravel, sand, or silt). Aquifers vary greatly in their characteristics. The s ...
s and in groundwater
Groundwater is the water present beneath Earth's surface in rock and Pore space in soil, soil pore spaces and in the fractures of stratum, rock formations. About 30 percent of all readily available fresh water in the world is groundwater. A unit ...
s in karst
Karst () is a topography formed from the dissolution of soluble carbonate rocks such as limestone and Dolomite (rock), dolomite. It is characterized by features like poljes above and drainage systems with sinkholes and caves underground. Ther ...
ic areas.
References
Further reading
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External links
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Fibrates
Phenol ethers
Carboxylic acids
CYP2C8 inhibitors
Drugs developed by Pfizer