Structure and biochemical effects of fenofibrate.
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.
Kloer
H U
HU
Department of Medicine, University of Giessen, Federal Republic of Germany.
D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005227:Fatty Acids / Q000096:biosynthesis*; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D011422:Propionates / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D010982:Platelet-Derived Growth Factor; D011422:Propionates; D014280:Triglycerides; D004247:DNA; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011345:Fenofibrate