TRC: Fibric acid derivatives

Fibric acid derivatives

Fibric acid derivatives or fibrates (gemfibrozil, ciprofibrate, and bezafibrate) belong to the group of triglyceride-lowering drugs that may be useful in lowering VLDL (and LDL), the so-called non-HDL goals. The mechanism of action of fibrates is very complex and not entirely understood. Their principal effect appears to be mediated through nuclear transcription factor peroxisome proliferator-activated receptor α (PPAR-α) in liver, adipose, and other tissues. Their agonist effect on these receptors up-regulates genes for apoA-I and A-II, SR-B1, fatty acid transport protein, fatty acid oxidation, and lipoprotein lipase. By increasing the activity of lipoprotein lipase, fibrates facilitate the transfer of triglycerides from VLDLs and chylomicrons into tissues.

Increased fatty acid oxidation reduces formation of VLDL triglycerides. Increased synthesis of apoA-I tends to raise HDL levels. The prominent effect of the fibrates is to reduce elevated triglyceride by 25-50% and secondarily to raise HDL by 15-25%.

Fibrates are generally well tolerated in most patients. GI complaints are the most common side effects. All drugs in this class appear to increase the likelihood of cholesterol gallstones. Additionally, the fibrates are highly bound to serum albumin and may displace warfarin, increasing its anticoagulant effects. Since fibrates are primarily excreted by the kidneys, caution should be observed in patients with renal failure. Myopathy has been observed particularly when combined with a statin.