What Are Fibrates?

Fibrates, also known as fibric acids, are a class of anti-atherosclerotic drugs. Clofibrate (also known as clofibrate) is the earliest fibrate derivative used in clinical practice. It has obvious lipid-lowering effects, but has many and serious adverse reactions. Newly-developed benzoic acid drugs such as gemfibrozil, bezazabate, fenofibrate, ciprobebate, etc. have strong effects and low toxicity.
Synthetic fibrates generally refer to phenoxy acids

Fibrates, also known as fibric acids, are a class of anti-atherosclerotic drugs. Clofibrate (also known as clofibrate) is the earliest fibrate derivative used in clinical practice. It has obvious lipid-lowering effects, but has many and serious adverse reactions. Newly-developed benzoic acid drugs such as gemfibrozil, bezazabate, fenofibrate, ciprobebate, etc. have strong effects and low toxicity.

Drug Name

Phenoxy acids

Alias

Bate

Foreign name

fibric acid

Whether prescription drugs

prescription

Whether to include health insurance

Incorporate

Phenoic acid pharmacological effects

Fibrates can significantly reduce plasma VLDL, and thus reduce TG, with a moderate decrease in LDL levels (a decrease of about 10%) and a certain increase in HDL levels. Experiments have confirmed that gemfibrozil can reduce the incidence of coronary heart disease, and can reduce the incidence of coronary heart disease in middle-aged men by about 1/3 compared with placebo, but does not improve overall survival ^[1] .

Mechanism of phenoxy acids

The mechanism of action of fibrates has not been fully elucidated. It may be related to their activation of LPL, which increases the hydrolysis of TG in CM and VLDL, and releases fatty acids stored in fat or metabolized in striated muscle. They also reduce VLDL production in the liver and increase LDL uptake by the liver.

In recent years, it has been confirmed that fibrates exert lipid-lowering effects by acting on peroxisome proliferator-activated receptors (PPARs). The receptor family has identified three subtypes of , / , and . PPAR increases HDL and decreases TG; PPAR decreases TG and improves insulin resistance; PPAR may increase HDL, reduce TG, and improve insulin resistance.

Among them, PPAR is the first identified PPARs family member, which is mainly expressed in liver and adipose tissue, and is also expressed in small amounts in kidney, heart, and skeletal muscle. Fibrates are ligands of PPAR. PPAR mediates the activation of fatty acid oxidation, increases the synthesis of LPL, reduces the expression of apcoC-II, and then increases the level of HDL-C. Glipidone is a high affinity ligand of PPAR, and has been widely used in the treatment of type 2 diabetes. PPARs have become eight points that regulate cardiovascular risk factors related to metabolic syndrome, and drug development aimed at improving these eight points is very active.

In addition to its effects on lipoproteins, fibrates can also reduce plasma C-reactive protein and fibrinogen, increase glucose tolerance, and inhibit vascular smooth muscle inflammation by inhibiting the expression of the transcription factor NF-B.

In addition, the drug also has anticoagulant, lower plasma viscosity, and strengthen fibrinolysis. These effects not related to lipid-lowering effects are also beneficial for the prevention and treatment of cardiovascular disease ^[1] .

Phenoxylic acid in vivo processes

Oral absorption of this class of drugs is rapid and complete, reaching the peak plasma concentration within 2-4 hours, and the plasma protein binding rate is 92% -96%. The half-lives are not exactly the same, with gemfibrizil yellow-stained benzabate for 1-2 hours, fenofibrate for 20 hours, and ciprobebate for 17-42 hours. Most are excreted from the urine as glucuronic acid conjugates.

Clinical application of phenoxy acids

For the treatment of patients with mixed dyslipidemia (such as elevated plasma TG and cholesterol) and patients with low HDL and high risk of atherosclerotic diseases (commonly in patients with type 2 diabetes), or the main cause of elevated TG or VLDV Idiopathic hyperlipidemia, such as type IIb, III, and IV hyperlipidemia, but it is not effective for patients with familial hyperchylidemia and elevated LDL. When the serum TG level is (2.26-5.65) mmol / L, fibrate drugs can be applied. If the serum TG level is elevated at (1.70-2.25) mmol / L, non-drug treatment can be used (such as diet control, weight loss, weight loss Drinking, etc.).

Phenoic acid adverse reactions

Myositis is not common, but once it occurs, it can be very serious and can cause rhabdomyolysis, causing myoglobinuria and renal failure, especially in patients who have kidney damage and those who are prone to hypertriglyceridemia. . Because statins can occasionally cause rhabdomyolysis, it is generally not recommended to use this drug in combination with statins.

In addition, fibrates can cause gastrointestinal reactions such as abdominal pain, diarrhea, and nausea, and most are well tolerated. A few patients have allergic reactions. It can be seen that mild transient liver aminotransferase elevation, liver function should be monitored early in the administration.

Because of its gallstone-causing effect, its use should be limited to patients who have undergone cholecystectomy.

Hepatic or renal dysfunction, pregnant women, lactating women and gallstone disease are contraindicated and used with caution in children.

This medicine is used in combination with oral anticoagulants, and the dose of anticoagulants should be appropriately reduced.

No statin has significantly improved the incidence and mortality of heart disease.