Etofibrate, like clofibrate, is a derivative of clofibric acid just like statins and nicotinic acids. In this context, they belong to the group of active substances known as lipid-lowering agents. Etofibrate is mainly effective in the case of an increased concentration of triglycerides. The lowering of cholesterol is less pronounced in this case.
What is etofibrate?
Etofibrate (chemical name: 2-hydroxymethylnicotinate), as the name suggests, is a fibrate that forms a group of drugs primarily used to treat what is known as hyperlipidemia (elevated blood lipids). Fibrates are mainly used to lower high levels of triglycerides, in contrast to statins, which are mainly used to treat high cholesterol. However, etofibrate also lowers cholesterol levels somewhat, but the main effect is on triglycerides. Etofibrate is thus one of the most important drugs for the treatment of disturbed metabolism of blood lipids and thus also for the treatment of cardiovascular diseases. Nevertheless, with other fibrates, etofibrate is only second choice, since statins are the lipid-lowering agents of first choice. Therefore, they should be used primarily when statins are not tolerated or when triglycerides are elevated. Etofibrate is a white, crystalline and insoluble powder and is given as a tablet or capsule daily. After absorption, etofibrate is converted back to clofibric acid and again excreted by the kidney. The dose should therefore be adjusted in renal insufficiency.
Pharmacologic effects on the body and organs
Etofibrate lowers the concentration of triglycerides. However, exactly how has not yet been adequately described. However, it is considered likely that etofibrate is responsible for the activation of PPARα, the peroxisome proliferator-activated receptor. This is a protein that, when activated, binds to cellular DNA and affects the formation of some proteins involved in lipid metabolism. This includes an increased degradation of LDL by 10 to 25 percent, and the increase of HDL by about 10 percent. LDL is the cholesterol that is deposited in the walls of the blood vessels, causing them to calcify and leading to atherosclerosis. In contrast, HDL is the cholesterol that is transported from the periphery to the liver, where it is broken down. In addition, etofibrate acts in the liver by reducing the release of VLDL, which is also a transport form of cholesterol, but this consists more of triglycerides. This occurs through impaired formation of cholesterol in the liver. Etofibrate also activates the enzyme lipoprotein lipase, which is essential for the breakdown of triglycerides in the blood. In addition to its effects on blood lipids, etofibrate also acts on other target structures, which is referred to as pleiotropic. These include improved vascular wall function, anti-inflammatory effects, and reduced formation of cytokines, which cause inflammatory processes. However, etofibrate also increases the lithogenicity of bile, which means that bile is at increased risk of forming cholesterol-containing gallstones.
Medicinal use and use for treatment and prevention.
Etofibrate has a broad use profile: it is used primarily in primary familial hypertriglyceridemia, a congenital metabolic disorder in which there are high levels of triglycerides in the blood. The most common cause is an enzyme defect, which leads to the breakdown of triglycerides. In addition to the primary form of hypertriglyceridemia, etofibrate is also used for the secondary form, i.e. the acquired form. Causes here include a high-fat diet, which can lead to obesity, as well as some metabolic disorders such as diabetes or renal insufficiency or inflammatory diseases of the kidney. Increased blood lipids can also be caused by therapeutic measures, when drugs are used that increase the plasma level of blood lipids. Examples include some hormones, beta blockers, or glucocorticoids. Etofibrate is also used in metabolic syndrome (also: “syndrome X”), a severe metabolic disorder involving several components. This disorder is also called the “Deadly Quartet” because it involves the four elements of impaired carbohydrate metabolism, elevated blood pressure, severe obesity, and impaired lipid metabolism with elevated levels of triglycerides and decreased levels of HDL.Etofibrate is taken several times a day and is prescribed in tablet or capsule form.
Risks and side effects
Etofibrate, like other fibrates, has a wide profile of side effects. These include some nonspecific side effects, such as an allergic reaction to etofibrate, among others. Like other allergic reactions, this is characterized by swelling, shortness of breath, and wheal formation. Furthermore, etofibrate can cause fever, chills, a flu-like feeling, as well as impotence, joint pain, headache, stomach pain, swelling of legs and ankles, dizziness and drowsiness. In addition, symptoms of the gastrointestinal tract may occur. These include general symptoms such as nausea, vomiting, diarrhea, and possible weight gain. Typical for therapy with etofibrate, but rather rarely the case, is rhabdomyolysis (muscle breakdown), which is characterized by muscle cramps, pain and weakness. Statins also cause rhabdomyolysis, so combination with etofibrate should be considered with caution. Furthermore, etofibrate also increases lithogenicity of bile, which is why there is an increased risk of developing gallstones. Etofibrate should not be taken in the presence of liver, gallbladder, or kidney disease. Also contraindicated are pregnancy and lactation.
