Changes in lipoprotein kinetics during therapy with fenofibrate and other fibric acid derivatives.

The fibric acid derivatives, including fenofibrate, significantly reduce very low-density lipoprotein triglyceride concentrations by stimulating lipoprotein lipase activity, thereby increasing very low-density lipoprotein catabolism. These agents may also reduce the hepatic secretion of nascent very low-density lipoprotein, but this effect is less consistent. Effects on low-density lipoprotein metabolism appear to depend upon the lipid disorder present before therapy. If hypertriglyceridemia and normal or low low-density lipoprotein levels are present, fibrate therapy is associated with a rise in low-density lipoprotein levels. This is due to a decreased fractional catabolism of low-density lipoprotein from an unusually high clearance to a more normal value. Treating pre-existing hypercholesterolemia usually results in a significant decrease in low-density lipoprotein levels. In this disorder, there is a demonstrable increase in low-density lipoprotein receptor-mediated clearance. It is not known at which site these drugs act to increase low-density lipoprotein receptor function in the latter patients. Some studies suggest that fibrate therapy increases high-density lipoprotein apolipoprotein AI production, but how this occurs has not been defined.