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.
Ginsberg
H N
HN
Columbia University College of Physicians and Surgeons, Department of Medicine, New York, New York 10032.
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001053:Apolipoproteins / Q000378:metabolism; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D011422:Propionates / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011422:Propionates; D008071:Lipoprotein Lipase; D002994:Clofibrate; D011345:Fenofibrate