clofibrate

Clofibrate is a lipid-lowering agent and the prototypical member of the fibrate class of drugs. It functions as a prodrug, being rapidly hydrolyzed in the body to its active form, clofibric acid. The primary mechanism of action involves the activation of the peroxisome proliferator-activated receptor alpha (PPARα), a nuclear receptor that regulates the expression of genes involved in fatty acid oxidation and lipoprotein metabolism. Activation of PPARα leads to increased activity of lipoprotein lipase, reduced synthesis of apolipoprotein C-III, and increased synthesis of apolipoproteins A-I and A-II, which collectively result in a significant reduction in plasma triglycerides (VLDL) and a modest increase in high-density lipoprotein (HDL) cholesterol. Originally developed by Imperial Chemical Industries (ICI) and approved for the treatment of various forms of hyperlipoproteinemia, clofibrate's clinical use has been largely discontinued in major markets, including the United States and Europe. This withdrawal followed findings from the WHO cooperative trial and other studies which indicated that while clofibrate reduced non-fatal cardiovascular events, it was associated with an increase in overall mortality, gallstones, and certain malignancies.

Brand names

Atromid-SClaripexLipavlon

Other names

clofibrateethyl 2-(4-chlorophenoxy)-2-methylpropionateclofibratoclofibratumethyl chlorophenoxyisobutyrate