Clofibrate is a derivative of clofibric acid and, along with statins and nicotinic acids, belongs to the group of active substances known as lipid-lowering agents. Clofibrate primarily lowers elevated plasma levels of triglycerides; the cholesterol-lowering effect is less pronounced.
What is clofibrate?
Clofibrate (chemical name: ethyl 2-(4-chlorophenoxy)-2-methylpropanoate) belongs to the group of fibrates, a group of drugs used primarily for drug therapy of elevated blood lipids. Unlike statins, which are used to treat elevated cholesterol levels, fibrates are also used to treat elevated triglycerides. This is also the main effect of fibrates. Thus, it is an important drug for the treatment of disturbed blood lipids and for the prevention of cardiovascular diseases. Clofibrate is a white, crystalline, insoluble powder that is taken daily in the form of tablets or capsules. Clofibrate is broken down by first being converted to clofibric acid and then excreted by the kidneys, which is why the dose must be adjusted in the case of kidney damage. Due to increased side effects, clofibrate is now rarely used and is no longer commercially available in Germany.
Pharmacologic effects on the body and organs
Clofibrate reduces plasma levels of triglycerides. The exact mechanism of action here is not yet fully explained. It is considered likely that clofibrate activates the so-called PPARα (peroxisome proliferator-activated receptor). This is a protein which, when activated, binds to DNA and thus leads to increased degradation of LDL cholesterol (10 – 25 %) and an increase in HDL cholesterol (approx. 10 %). LDL is the colloquially known “bad” cholesterol, which likes to be deposited on the walls of blood vessels, leading to atherosclerosis. Meanwhile, HDL is the so-called “good” cholesterol, which is transported to the liver and broken down there. Another effect of clofibrate is the impaired formation of cholesterol in the liver, as well as a reduced release of VLDL from the liver. VLDL, similar to LDL, transports cholesterol formed in the liver from the liver to other organs. Unlike LDL, VLDL consists more of triglycerides and is thus involved in atherosclerotic processes. In addition, clofibrate enhances the activity of the enzyme lipoprotein lipase, which is important for the breakdown of triglycerides. Similar to statins, pleiotropic effects are also observed under clofibrate, which means that different effects are induced on different target structures. These include reduced formation of inflammatory proteins as well as improved vessel wall function and inflammatory changes in these due to atherosclerotic processes. A negative effect of clofibrate is the increased excretion of cholesterol into the bile, resulting in the increased risk of cholesterol gallstones.
Medical use and use for treatment and prevention.
Clofibrate, as well as other fibrates, is used primarily in primary familial hypertriglyceridemia. This is a metabolic disorder in which there are unphysiologically high levels of triglycerides in the blood. It is called ‘primary familial’ because it is a congenital excess of triglycerides. In most cases, the cause is a defect in an enzyme that is important for breaking down triglycerides. However, in addition to the familial form of hypertriglyceridemia, clofibrate is also used in the secondary form, i.e. in the acquired form. This can have various causes, such as poor nutrition (obesity, anorexia), metabolic disorders (for example, diabetes mellitus), and kidney diseases such as nephrotic syndrome or kidney failure. Misuse of medications can also be the cause of secondary hypertriglyceridemia and thus represent an indication for lipid-lowering drugs. Such drugs that cause elevated plasma levels of blood lipids include beta-blockers, cortisone, or some hormones. Clofibrate can also be used in the so-called metabolic syndrome, which is also called “syndrome X” or the “fatal quartet”. This is a dangerous combination of disturbed sugar metabolism, elevated blood pressure, elevated triglycerides combined with low HDL cholesterol and severe obesity.Clofibrate is a whitish, crystalline powder that the patient must take several times a day in the form of tablets and capsules. However, since it has been taken off the market in Germany due to increased side effects, other fibrates such as bezafibrate or fenofibrate, which are also (like clofibrate) derivatives of clofibric acid, are more commonly prescribed.
Risks and side effects
Clofibrate has a wide range of side effects. Nonspecific side effects include allergic reactions to the drug characterized by swelling, difficulty breathing, and hives. Other side effects include fever and chills, flu-like feeling, swelling of legs and ankles, and joint pain, impotence, headache, dizziness and lightheadedness, and sudden weight gain. More specific side effects typical of fibrate therapy include muscle cramps, muscle pain, and muscle weakness due to rhabdomyolysis (muscle breakdown). Therefore, combination therapy with statins should be well considered and controlled, as they also cause muscle breakdown. Furthermore, clofibrate causes gastrointestinal problems such as nausea, vomiting and diarrhea. Clofibrate also increases the risk of gallstones. Under no circumstances should clofibrate be taken if you have liver or gallbladder disease, or if you have kidney weakness, are pregnant, or are breastfeeding.
