Hans U. Kloer
Nov 27, 1987
Citations
0
Influential Citations
30
Citations
Quality indicators
Journal
The American journal of medicine
Abstract
The structures of various fibric acid derivatives are compared. Fenofibrate inhibits de novo hepatic fatty acid synthesis and seems to inhibit hepatic very low-density lipoprotein synthesis, but it enhances mitochondrial and peroxisomal fatty acid oxidation and lipoprotein lipase activity. It produces a very significant reduction in the plasma triglyceride concentration. Fenofibrate also inhibits cholesterol synthesis prior to processing mevalonate, indirectly causing significant reduction of hydroxymethylglutaryl coenzyme A reductase activity. The drug may inhibit acyl-coenzyme A-cholesterol transferase activity, reducing cholesterol ester accumulation within cells. Fenofibrate significantly increases the fractional rate of lecithin-cholesterol acyltransferase activity in normolipidemic and hypercholesterolemic patients. This may explain the increase in cholesterol ester levels observed in high-density lipoproteins. It may stimulate bile acid synthesis from exogenous cholesterol. It causes a marked reduction of increased spontaneous platelet aggregation. Fenofibrate also markedly diminishes the effect of platelet-derived growth factor upon DNA synthesis in vitro, an effect that might impede a key event in early atherogenesis. Thus, fenofibrate has effects not directly related to its lipid- and lipoprotein-lowering action.