QuickView for Clofibrate (compound)

Summary
General Info

PubChem

PubChem Compound 254788

Name:	Clofibrate
PubChem Compound ID:	254788
Description:	A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)
Molecular formula:	C₃₁H₄₅ClO₅
Molecular weight:	533.139 g/mol
Synonyms:	8075-95-4; Atromid; 3-.alpha.-hydroxy-5-.alpha.-androstan-17-one, mixture with ethyl 2- (4-chlorophenoxy)-2-methylpropanoate; Atromid (Ayerst 647); 5.alpha.-Androstan-17-one, 3.alpha.-hydroxy-, compd. with propionic acid, 2-(p-chlorophenoxy)-2-methyl-, ethyl ester; NSC79390

DrugBank

Identification

Name:	Clofibrate
Name (isomeric):	DB00636
Drug Type:	small molecule
Description:	A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)
Synonyms:	Ethyl para-chlorophenoxyisobutyrate; Chlorfenisate; EPIB; Chlorphenisate; Ethyl p-chlorophenoxyisobutyrate; Clofibate; CPIB; Ethyl clofibrate; Clofibratum; Ethyl chlorophenoxyisobutyrate. show more » Ethyl para-chlorophenoxyisobutyrate; Chlorfenisate; EPIB; Chlorphenisate; Ethyl p-chlorophenoxyisobutyrate; Clofibate; CPIB; Ethyl clofibrate; Clofibratum; Ethyl chlorophenoxyisobutyrate; Clofibrato show less «
Brand:	Dura clofibrat, Angiokapsul, Clobrat, Clobren-SF, Atheropront, Miscleron, Sklerepmexe, Skleromex, Clofibrat, Sklero-Tablinen, Clofibram, Yoclo, Levatrom, Lipidsenker, Lipide 500, Delipid, Arterosol, Hyclorate, Liposid, Ticlobran, Sklero-tablinene, Claripex, Lipomid, Liprinal, Liporil, Arterioflexin, Claripex CPIB, Xyduril, Cartagyl, Lipofacton, Atheromide, neo-Atomid, Atrovis, Scrobin, Amotril S, Athranid-Wirkstoff, Negalip, Antilipide, Regelan, Tetrasipton, Anparton, Regelan N, Atromid-S, Klofiran, Atromida, Citiflus, Bioscleran, Ateriosan, Serofinex, Clofipront, Liponorm, Normat, Vincamin compositum, Atromidin, Liporeduct, Antilipid, Thiosan, Fibralem, Athebrate, Clofinit, Normalip, Clofar, Apolan, ELPI, Artevil, Azionyl, Artes, Novofibrate, Lipavlon, Lipamid, Lipavil, Sklerolip, Atromid, Gerastop, Serotinex, Robigram, Sklero, Persantinat, Klofibrat, Skerolip, Deliva, Oxan 600, Neo-Atromid, Sklero-tabuls, Liprin, Atrolen, Regardin, Clobren-5F, Thillate, Ateculon, Bresit, Skleromexe, Atromid S, Normolipol, Cloberat, Lobetrin, Amotril
Category:	Antilipemic Agents, Anticholesteremic Agents
CAS number:	637-07-0

Pharmacology

Indication:	For Primary Dysbetalipoproteinemia (Type III hyperlipidemia) that does not respond adequately to diet. This helps control high cholesterol and high triglyceride levels.
Pharmacology:	Clofibrate is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (S_f 20-400) rich in triglycerides. Serum cholesterol may be decreased, particularly in those patients whose cholesterol elevation is due to the presence of IDL as a result of Type III h... show more » Clofibrate is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (S_f 20-400) rich in triglycerides. Serum cholesterol may be decreased, particularly in those patients whose cholesterol elevation is due to the presence of IDL as a result of Type III hyperlipoproteinemia. Several investigators have observed in their studies that clofibrate may produce a decrease in cholesterol linoleate but an increase in palmitoleate and oleate, the latter being considered atherogenic in experimental animals. The significance of this finding is unknown at this time. Reduction of triglycerides in some patients treated with clofibrate or certain of its chemically and clinically similar analogs may be associated with an increase in LDL cholesterol. Increase in LDL cholesterol has been observed in patients whose cholesterol is initially normal. Animal studies suggest that clofibrate interrupts cholesterol biosynthesis prior to mevalonate formation. show less «
Mechanism of Action:	Clofibrate increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Clofibrate also inhibits ... show more » Clofibrate increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Clofibrate also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. Also, as a fibrate, Clofibrate is an agonist of the PPAR-α receptor[4] in muscle, liver, and other tissues. This agonism ultimately leads to modification in gene expression resulting in increased beta-oxidation, decreased triglyceride secretion, increased HDL, increased lipoprotein lipase activity. show less «
Absorption:	Completely but slowly absorbed from the intestine. Between 95% and 99% of an oral dose of clofibrate is excreted in the urine as free and conjugated clofibric acid; thus, the absorption of clofibrate is virtually complete.
Protein binding:	Highly protein-bound (95% to 97%).
Biotransformation:	Hepatic and gastrointestinal: rapid de-esterification occurs in the gastrointestinal tract and/or on first-pass metabolism to produce the active form, clofibric acid (chlorophenoxy isobutyric acid [CPIB]).
Half Life:	Half-life in normal volunteers averages 18 to 22 hours (range 14 to 35 hours) but can vary by up to 7 hours in the same subject at different times.
Toxicity:	Oral, mouse: LD₅₀ = 1220 mg/kg; Oral, rabbit: LD₅₀ = 1370 mg/kg; Oral, rat: LD₅₀ = 940 mg/kg. No reported case of overdosage in humans.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take with food, since it may reduce gastric irritation.

Drug interaction:

Acetohexamide	Clofibrate may increase the effect of sulfonylurea, acetohexamide.
Insulin Aspart	Increases the effect of insulin
Gliclazide	Clofibrate may increase the effect of sulfonylurea, gliclazide.
Tolazamide	Clofibrate may increase the effect of sulfonylurea, tolazamide.
Insulin Detemir	Increases the effect of insulin

Targets

Peroxisome proliferator-activated receptor alpha

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids

UniProt ID:

Q07869

Gene:

PPARA

Actions:

agonist

References:

Barclay TB, Peters JM, Sewer MB, Ferrari L, Gonzalez FJ, Morgan ET: Modulation of cytochrome P-450 gene expression in endotoxemic mice is tissue specific and peroxisome proliferator-activated receptor-alpha dependent. J Pharmacol Exp Ther. 1999 Sep;290(3):1250-7.
View Article

Murata M, Kaji H, Takahashi Y, Iida K, Mizuno I, Okimura Y, Abe H, Chihara K: Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro. Biochem Biophys Res Commun. 2000 Apr 13;270(2):343-8.
View Article

Hunt MC, Lindquist PJ, Peters JM, Gonzalez FJ, Diczfalusy U, Alexson SE: Involvement of the peroxisome proliferator-activated receptor alpha in regulating long-chain acyl-CoA thioesterases. J Lipid Res. 2000 May;41(5):814-23.
View Article

Casas F, Domenjoud L, Rochard P, Hatier R, Rodier A, Daury L, Bianchi A, Kremarik-Bouillaud P, Becuwe P, Keller J, Schohn H, Wrutniak-Cabello C, Cabello G, Dauca M: A 45 kDa protein related to PPARgamma2, induced by peroxisome proliferators, is located in the mitochondrial matrix. FEBS Lett. 2000 Jul 28;478(1-2):4-8.
View Article

Komuves LG, Hanley K, Lefebvre AM, Man MQ, Ng DC, Bikle DD, Williams ML, Elias PM, Auwerx J, Feingold KR: Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo. J Invest Dermatol. 2000 Sep;115(3):353-60.
View Article

Gelosa P, Banfi C, Gianella A, Brioschi M, Pignieri A, Nobili E, Castiglioni L, Cimino M, Tremoli E, Sironi L: PPAR-alpha agonism prevents the oxidative stress and inflammatory processes involved in brain and renal damage in stroke-prone rats. J Pharmacol Exp Ther. 2010 Jul 29.
View Article

Palkar PS, Anderson CR, Ferry CH, Gonzalez FJ, Peters JM: Effect of prenatal peroxisome proliferator-activated receptor alpha (PPARalpha) agonism on postnatal development. Toxicology. 2010 Jul 15.
View Article

Enzymes

Cytochrome P450 2E1

Glutathione S-transferase A2