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a drug (trade name Atromid-S) that reduces lipids in the blood serum; used to treat some cardiovascular diseases (同)Atromid-S

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/02 17:22:18」(JST)

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Clofibrate (tradename Atromid-S) is an organic compound. It is marketed as a fibrate. It is a lipid-lowering agent used for controlling the high cholesterol and triacylglyceride level in the blood. It increases lipoprotein lipase activity to promote the conversion of VLDL to LDL, and hence reduce the level of VLDL. It can increase the level of HDL as well.

Complications and controversies

It can induce SIADH, syndrome of inappropriate secretion of antidiuretic hormone ADH (vasopressin).

The World Health Organization Cooperative Trial on Primary Prevention of Ischaemic Heart Disease using clofibrate to lower serum cholesterol observed excess mortality in the clofibrate-treated group despite successful cholesterol lowering (47% more deaths during treatment with clofibrate and 5% after treatment with clofibrate) than the non-treated high cholesterol group. These deaths were due to a wide variety of causes other than heart disease, and remain "unexplained".^[1]

Clofibrate was discontinued in 2002 due to adverse affects.

References

^ "WHO cooperative trial on primary prevention of ischaemic heart disease with clofibrate to lower serum cholesterol: final mortality follow-up. Report of the Committee of Principal Investigators". Lancet 2 (8403): 600–4. September 1984. PMID 6147641.

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1. フィブラート系薬剤による脂質低下 lipid lowering with fibric acid derivatives
2. クリグラー・ナジャー症候群 crigler najjar syndrome
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English Journal

Tissue-specific differential induction of duplicated fatty acid-binding proteingenes by the peroxisome proliferator, clofibrate, in zebrafish (

Venkatachalam AB, Lall SP, Denovan-Wright EM, Wright JM.AbstractABSTRACT: BACKGROUND: Force, Lynch and Conery proposed the duplication-degeneration-complementation (DDC) model in which partitioning of ancestral functions (subfunctionalization) and acquisition of novel functions (neofunctionalization) were the two primary mechanisms for the retention of duplicated genes. The DDC model was tested by analyzing the transcriptional induction of the duplicated fatty acid-binding protein (fabp) genes by clofibrate in zebrafish. Clofibrate is a specific ligand of the peroxisome proliferator-activated receptor (PPAR); it activates PPAR which then binds to a peroxisome proliferator response element (PPRE) to induce the transcriptional initiation of genes primarily involved in lipid homeostasis. Zebrafish was chosen as our model organism as it has many duplicated genes owing to a whole genome duplication (WGD) event that occurred ~230-400 million years ago in the teleost fish lineage. We assayed the steady-state levels of fabp mRNA and heterogeneous nuclear RNA (hnRNA) transcripts in liver, intestine, muscle, brain and heart for four sets of duplicated fabp genes, fabp1a/fabp1b.1/fabp1b.2, fabp7a/fabp7b, fabp10a/fabp10b and fabp11a/fabp11b in zebrafish fed different concentrations of clofibrate. Result: Electron microscopy showed an increase in the number of peroxisomes and mitochondria in liver and heart, respectively, in zebrafish fed clofibrate. Clofibrate also increased the steady-state level of acox1 mRNA and hnRNA transcripts in different tissues, a gene with a functional PPRE. These results demonstrate that zebrafish is responsive to clofibrate, unlike some other fishes. The levels of fabp mRNA and hnRNA transcripts for the four sets of duplicated fabp genes was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR). The level of hnRNA coded by a gene is an indirect estimate of the rate of transcriptional initiation of that gene. Clofibrate increased the steady-state level of fabp mRNAs and hnRNAs for both the duplicated copies of fabp1a/ fabp1b.1, and fabp7a/fabp7b, but in different tissues. Clofibrate also increased the steady-state level of fabp10a and fabp11a mRNAs and hnRNAs in liver, but not for fabp10b and fabp11b. CONCLUSION: Some duplicated fabp genes have, most likely, retained PPREs, but induction by clofibrate is over-ridden by an, as yet, unknown tissue-specific mechanism(s). Regardless of the tissue-specific mechanism(s), transcriptional control of duplicated zebrafish fabp genes by clofibrate has markedly diverged since the WGD event.
BMC evolutionary biology.BMC Evol Biol.2012 Jul 9;12(1):112. [Epub ahead of print]
ABSTRACT: BACKGROUND: Force, Lynch and Conery proposed the duplication-degeneration-complementation (DDC) model in which partitioning of ancestral functions (subfunctionalization) and acquisition of novel functions (neofunctionalization) were the two primary mechanisms for the retention of duplicat
PMID 22776158

Inhibitors of 20-hydroxyeicosatetraenoic acid (20-HETE) formation attenuate the natriuretic effect of dopamine.

Fernandez MM, Gonzalez D, Williams JM, Roman RJ, Nowicki S.SourceCentro de Investigaciones Endocrinólogicas (CEDIE-CONICET), Gallo 1360, C1425EFD Buenos Aires, Argentina.
European journal of pharmacology.Eur J Pharmacol.2012 Jul 5;686(1-3):97-103. Epub 2012 May 2.
Endogenous renal dopamine is a major physiological regulator of renal ion transport; however its intracellular signaling pathways are not thoroughly understood. The present study examined the role of 20-hydroxyeicosatetraenoic acid (20-HETE), the major cytochrome P450 (CYP4A) metabolite of arachidon
PMID 22575524

Japanese Journal

Altered expression of GADD45 genes during the development of chemical-mediated liver hypertrophy and liver tumor promotion in rats

OZAWA Shogo,GAMOU Toshie,HABANO Wataru,INOUE Kaoru,YOSHIDA Midori,NISHIKAWA Akiyoshi,NEMOTO Kiyomitsu,DEGAWA Masakuni
Journal of toxicological sciences 36(5), 613-623, 2011-10-01
… Five-week-old male rats were fed a basal diet or a diet containing phenobarbital (PB) or clofibrate (CF) for 3 days, 4 weeks, and 13 weeks. …
NAID 10029481415

Super-induced gene expression of the N-methyl-D-aspartate receptor 2C subunit in chemical-induced hypertrophic liver in rats

NEMOTO Kiyomitsu,TANAKA Takahiro,IKEDA Ayaka,ITO Sei,MIZUKAMI Masanori,HIKIDA Tokihiro,GAMOU Toshie,HABANO Wataru,OZAWA Shogo,INOUE Kaoru,YOSHIDA Midori,NISHIKAWA Akiyoshi,DEGAWA Masakuni
Journal of toxicological sciences 36(5), 507-514, 2011-10-01
… To identify gene expression that can be closely involved in chemical-induced hepatocellular hypertrophy, the hepatic gene expression profile was assessed by cDNA microarray analysis in male F344 rats fed for 3 days, 4 weeks, and 13 weeks a diet containing a hepatocellular hypertrophy inducer, either phenobarbital (500 ppm), clofibrate (2,500 ppm), or piperonyl butoxide (20,000 ppm). …
NAID 10029481028

Related Pictures

★リンクテーブル★

リンク元	「フィブラート系薬物」「クロフィブラート」「fibrate」「clofibric acid」
拡張検索	「aluminum clofibrate」「aluminium clofibrate」

「フィブラート系薬物」

Clofibrate
Systematic (IUPAC) name
	ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy; category	AU: B1; US: C (Risk not ruled out);
Legal status	US: Discontinued;
Routes of; administration	Oral
Pharmacokinetic data
Protein binding	Variable, 92–97% at therapeutic concentrations
Metabolism	Hydrolyzed to clofibric acid; hepatic glucuronidation
Half-life	Highly variable; average 18–22 hours. Prolonged in renal failure
Excretion	Renal, 95 to 99%
Identifiers
CAS Registry Number	637-07-0
ATC code	C10AB01
PubChem	CID 2796
DrugBank	DB00636
ChemSpider	2694
UNII	HPN91K7FU3
KEGG	D00279
ChEBI	CHEBI:3750
ChEMBL	CHEMBL565
Chemical data
Formula	C12H15ClO3
Molecular mass	242.698 g/mol
	SMILES Clc1ccc(OC(C(=O)OCC)(C)C)cc1;
	InChI InChI=1S/C12H15ClO3/c1-4-15-11(14)12(2,3)16-10-7-5-9(13)6-8-10/h5-8H,4H2,1-3H3 ; Key:KNHUKKLJHYUCFP-UHFFFAOYSA-N ;
Physical data
Boiling point	148 °C (298 °F)
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同: フィブラート系リポ蛋白代謝改善薬
関: フィブラート

概念

Fibrates such as clofibrate and gemfibrozil act mainly to lower plasma triacylglycerols by decreasing the secretion of triacylglycerol and cholesterol-containing VLDL by the liver. In addition, they stimulate hydrolysis of VLDL triacylglycerols by lipoprotein lipase. (harper)