Detail of "54419-31-7"

Reference

New developments concerning the mode of action of fenofibrate

New developments concerning the mode of action of fenofibrate. Chazan, Jean Bernard (Cent. Rech. Daix, Lab. Fournier, Fontaine-les-Dijon 21121, Fr.). Treat. Hyperlipoproteinemia, 171-4. Edited by: Carlson, Lars A.; Olsson, Anders G. Raven: New York, N. Y. (English) 1984. CODEN: 51OOAE. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacology) Studies into the mechanism of the antiatherosclerosis activity of fenofibrate (I) [49562-28-9] are described in rats. Treatment of rats with I or its metabolite LF433 [54419-31-7] for 3-12 wk inhibited hepatic microsomal HMG-CoA reductase [9028-35-7] activity. Also, treatment with I or fenofibric acid [42017-89-0] restored blood platelet aggregation to normal in former breeder rats, a model of platelet hyperactivity. In smooth muscle cells from aortas of rats, platelet-derived growth factor-induced smooth muscle cell proliferation in the intima was inhibited by fenofibric acid in a non-competitive fashion along a cholesterol-independent mechanism.

Effect of fenofibrate and LF 2151 on hepatic peroxisomes in hamsters

Effect of fenofibrate and LF 2151 on hepatic peroxisomes in hamsters. Pourbaix, Suzanne; Heller, Francis; Harvengt, Carl (Lab. Pharmacother., Univ. Cathol. Louvain, Brussels B-1200, Belg.). Biochem. Pharmacol., 33(22), 3661-6 (English) 1984. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Hamsters were given a diet contg. fenofibrate (I) [49562-28-9] (0.5% or 0.05%) or its metabolite LF 2151 (II) [54419-31-7] (0.15% or 0.015%) or a std. diet for a 3-wk period. At the end of this period, the anal. of plasma lipids showed that the mean plasma triglyceride concns. were not significantly different in the 5 groups of animals. The mean plasma cholesterol [57-88-5] concns. were significantly reduced in animals treated with both drugs but only when given at the high dosage. No consistent changes were noted in the liver wt./body wt. ratio and the DNA content of the liver; the no. of peroxisomes was increased in the hepatocytes of animals given fenofibrate at the high dosage. Liver homogenates were fractionated and the fractions rich in peroxisomes were used for assays of several enzymes involved in lipid metab. Compared with the control animals, activity of cyanide-insensitive fatty acyl-CoA (FA-CoA) oxidizing system was significantly increased by fenofibrate at the high dosage, carnitine acetyltransferase [9029-90-7] activity was markedly increased by both drugs at the high dosage and catalase [9001-05-2] activity remained unmodified. As there was a significant inverse correlation between the peroxisomal activity of FA-CoA oxidizing system and the plasma cholesterol concns., it is suggested that the increase of peroxisomal b-oxidn. activity can be involved in the hypocholesterolemic action of fenofibrate and LF 2151. This is further substantiated by the finding that fenofibrate and LF 2151 were present in the oxidizing system. The presence of fenofibric acid [42017-89-0] in the plasma of hamsters given LF 2151 suggested that hepatocytes are able to generate the parent drug from this metabolite, underlining that the pharmacokinetics of fenofibrate are rather complex in hamsters.