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Product Details:

  • Product Name: Clofibrate
  • CAS #: 637-07-0
  • Mode 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 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-_ 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.

  • Pharmacodynamics:

    Clofibrate is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (Sf 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.

  • Metabolism:

    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]).

  • 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.

  • IUPAC: ethyl 2-(4-chlorophenoxy)-2-methylpropanoate
  • ATC: C10AB01 C10AB03
  • PubChem: 2796
  • DrugBank: DB00636 (APRD00879)
  • Formula: C62H86N12O16
  • Molecular Mass: 242.699
  • Synonyms: Chlorfenisate Chlorphenisate Clofibate Clofibrato Clofibratum CPIB EPIB Ethyl chlorophenoxyisobutyrate Ethyl clofibrate Ethyl p-chlorophenoxyisobutyrate Ethyl para-chlorophenoxyisobutyrate
  • SMILES: CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1
  • InChl: KNHUKKLJHYUCFP-UHFFFAOYSA-N
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