Clofibrate

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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%

Uses

  • Different kinds of hyperlipidemias (type III)
  • Regression of xanthomas
  • Dysbetalipoproteinemia
  • Hypertriglyceridemias
  • MI
  • Mobilizes cholesterol from storage sites and decreases incidence of coronary heart diseases by 50%, when used for prolonged time.

Pharmacokinetics

Absorption

Absorbed after oral administration. Bioavailability is increased with food.

PPC

Plasma peak concentration is achieved in 3-4 hours

PPB

Extensively bound to plasma proteins

Excretion

Metabolized in liver and predominantly eliminated in urine.

Adverse effects

May produce:

  1. GIT disturbances
  2. Allergic reactions
  3. 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.
  4. Can produce hypokalemias
  5. Clofibrate produces blood dyscrasias and cardiac arrhythmias
  6. In experimental animals, found to be teratogenic
  7. Liver injuries
  8. Can displace oral anticoagulants from protein binding sites
  9. Can enhance toxicity of warfarin
  10. Increases the incidence of gall stones as increases the secretion of cholesterol in bile.
  11. Decreases the conversion of cholesterol into bile acids, so chances of gall stones are more.
  12. Cholelithiasis
  13. Anemias, decreases WBC count
  14. Hair loss

Contraindications

  1. Pregnancy
  2. Liver disease
  3. Gall stones
  4. Renal failure
  5. Alcohol
  6. Children

Dose

300 mg, which may be increased up to 600 mg, twice or thrice daily, depending upon the severity of disease. Usually taken with meals.

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The writer enjoys medical education and has special interest in community medicine.