Clofibrate is the first lipid lowering drug discovered, but rarely used because of toxic effects. Better drugs with less toxicity and more effects are available.
It acts by:
- Stimulating activity of lipoprotein lipase enzyme involved in breakdown of triglycerides. In this way, TGs are decreased.
- Acting as an agonist at PPAR alpha receptor (peroxisome proliferated activated receptor alpha), involved in fatty acid metabolism.
- Fibric acid derivatives also cause up and down regulation of genes involved in fatty acid metabolism
Upregulation of apolipoprotein alpha 1 gene and down regulation of apolipoprotein C2 gene occurs, so produces hypolipidemic effects. Also increases
- LDL receptor expression in liver under effect of PPAR alpha. More extraction of LDL from plasma occurs.
- Also decrease TGs synthesis by liver.
- Decrease TGs by 40-60%
- Decrease LDL, but to a lesser extent 10-15%
- Increase HDL by 10-25%
- Different kinds of hyperlipidemias (type III)
- Regression of xanthomas
- Mobilizes cholesterol from storage sites and decreases incidence of coronary heart diseases by 50%, when used for prolonged time.
Absorbed after oral administration. Bioavailability is increased with food.
Plasma peak concentration is achieved in 3-4 hours
Extensively bound to plasma proteins
Metabolized in liver and predominantly eliminated in urine.
- GIT disturbances
- Allergic reactions
- Myopathies especially when combined with HMG CoA reductase inhibitors (muscle weakness, tenderness and cramps), less frequently with Fenofibrates. (Rosuvastin amongst statins has lesser incidence of myopathies.
- Can produce hypokalemias
- Clofibrate produces blood dyscrasias and cardiac arrhythmias
- In experimental animals, found to be teratogenic
- Liver injuries
- Can displace oral anticoagulants from protein binding sites
- Can enhance toxicity of warfarin
- Increases the incidence of gall stones as increases the secretion of cholesterol in bile.
- Decreases the conversion of cholesterol into bile acids, so chances of gall stones are more.
- Anemias, decreases WBC count
- Hair loss
- Liver disease
- Gall stones
- Renal failure
300 mg, which may be increased up to 600 mg, twice or thrice daily, depending upon the severity of disease. Usually taken with meals.