They are better absorbed when taken on empty stomach, than when taken with food Fibric acid derivations (Fibrates) The class includes:? - Bezafibrate - Ciprofibrate - Fenofibrate and - Getnfibrozil The original fibrate clofibrate is obselete. Mechanism of action: The.4, drugs act by activating lipoprotein lipase which is a key enzyme in the degradation of VLDL. This effect is exeed through nuclear receptor, PPAR a (peroxisome proliferators activated receptor alpha) - The PPAR a are class of intracellular receptor that modulate carbohydrate and fat metabolism and adipose tissue differentiation. Major effect of the fibrates is to reduce triglycerides TG (contained in VLDL) and to increase HDL. Fibrates also reduce plasma fibrinogen level. They are first line drugs in dysbetalipoproteinenzias and hyperiglyceridimias Pharmacokinetics of fibrates:? Fibric acid derivatives are well absorbed from the gastrointestinal tract, extensively bound to plasma proteins and are excreted mainly by the kidney as unchanged drug or metabolite. Absorption of fibrates in improved when the drug in taken with food. They are contraindicated when hepatic or renal function is severely impaired. Adverse effects of fibrates:? Fibrates can induce a myositis like syndrome, the risk is greater in patient with poor renal function and in those who are also receiving a statin. Other adverse effects include rashes, gastrointestinal symptoms, arryhthmias, hypokalenzia and high blood level of aminotransferases or alkaline phosphatase. Some more features of fibrates Fenofibrate is a prodrug with longest half life. It has miximum LDL cholesterol lowering action. Clofibrate is not used now becuase it results in increased moality (due to malignancies and post cholecystectomy) complications and did not prevent fatal MI.