Mechanism of Action

Lipid Triad: Role of PPARα Activation in Lipid Metabolism

Lipid Metabolism (1)

TriCor® ( fenofibrate tablets) Mechanism of Action (2)

• Fenofibric acid, the metabolite of fenofibrate, activates peroxisome proliferator-activated receptor α (PPARα).
• Fenofibrate increases lipolysis and elimination of TG-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity).*
• The resulting fall in TG produces an alteration in the size and composition of LDL from small dense particles (which are thought to be atherogenic due to their susceptibility to oxidation) to large buoyant particles. Large buoyant particles have a greater affinity for cholesterol receptors and are catabolized rapidly.*
• In types IIa and IIb hyperlipidemia, LDL-C decreases; in type IV hyperlipidemia, LDL-C often increases.
• Activation of PPARα also induces an increase in the synthesis of apoproteins A-I and A-II, and
  HDL-C.*
• Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid.

References

1. Adapted from Witztum JL. In: Hardman JG, Limbird LE, Monlinoff PB, Ruddon RW, Gilman AG, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1996:876-878.
2. TriCor tablets package insert, Abbott Laboratories.